Soft condensed matter physics of foods and macronutrients

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Understanding food properties is paramount for enhancing features such as appearance, taste and texture, for improving health-related factors such as minimizing the onset of allergies or improving the digestibility of nutrients, and for preserving food and extending its shelf-life. This Review discusses the challenges and opportunities offered by analysing foods as soft condensed matter systems. Emphasis is placed on the three main macronutrients constituting the main building blocks of foods: polysaccharides, proteins and lipids. Similarities and differences with synthetic polymers, colloids and surfactants are described. This Review also discusses the lessons that can be learned from soft matter approaches and the extent of their applicability to real foods.

Key points

  • The theoretical tools developed in soft condensed matter physics provide a means to describe foods and macronutrients at scales ranging from angstroms to tens of micrometres.

  • Polymer physics can be used to characterize the properties of polysaccharides and unfolded proteins, whose complex nature poses unusual theoretical questions.

  • Dispersions and gels based on proteins can be described by the physics of colloids and aggregates, and their phase diagrams can be rationalized accordingly.

  • The structural properties of food emulsions and targeted delivery of macronutrients from lipid-based mesostructures can be studied and controlled with the aid of surfactant physics and transport theory.

  • Some experimental soft matter tools are currently underexploited in food science, which calls for further theoretical research in soft condensed matter physics.

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Fig. 1: Overview of the systems discussed.
Fig. 2: Definitions of single-polymer physics.
Fig. 3: Applications of single-polymer physics concepts to protein systems and polysaccharides.
Fig. 4: Physics of colloids and aggregates applied to food systems.
Fig. 5: Topological and geometrical features of some common inverse lipid mesophases.
Fig. 6: Physics of lipid mesophases.


  1. 1.

    Mezzenga, R., Schurtenberger, P., Burbidge, A. & Michel, M. Understanding foods as soft materials. Nat. Mater. 4, 729–740 (2005).

  2. 2.

    Dominguez-Hernandez, E., Salaseviciene, A. & Ertbjerg, P. Low-temperature long-time cooking of meat: eating quality and underlying mechanisms. Meat Sci. 143, 104–113 (2018).

  3. 3.

    McClements, D. J. Edible nanoemulsions: fabrication, properties, and functional performance. Soft Matter 7, 2297–2316 (2011).

  4. 4.

    Lett, A. M., Yeomans, M. R., Norton, I. T. & Norton, J. E. Enhancing expected food intake behaviour, hedonics and sensory characteristics of oil-in-water emulsion systems through microstructural properties, oil droplet size and flavour. Food Qual. Prefer. 47, 148–155 (2016).

  5. 5.

    Chiappisi, L. & Grillo, I. Looking into limoncello: the structure of the Italian liquor revealed by small-angle neutron scattering. ACS Omega 3, 15407–15415 (2018).

  6. 6.

    Gallo, P. et al. Water: a tale of two liquids. Chem. Rev. 116, 7463–7500 (2016).

  7. 7.

    Barnes, P., Finney, J. L., Nicholas, J. D. & Quinn, J. E. Cooperative effects in simulated water. Nature 282, 459–464 (1979).

  8. 8.

    Luzar, A. & Chandler, D. Hydrogen-bond kinetics in liquid water. Nature 379, 55–57 (1996).

  9. 9.

    Poole, P. H., Sciortino, F., Essmann, U. & Stanley, H. E. Phase behaviour of metastable water. Nature 360, 324–328 (1992).

  10. 10.

    Palmer, J. C., Poole, P. H., Sciortino, F. & Debenedetti, P. G. Advances in computational studies of the liquid–liquid transition in water and water-like models. Chem. Rev. 118, 9129–9151 (2018).

  11. 11.

    Urbic, T. & Dill, K. A. Water is a cagey liquid. J. Am. Chem. Soc, (2018).

  12. 12.

    Nomura, K. et al. Evidence of low-density and high-density liquid phases and isochore end point for water confined to carbon nanotube. Proc. Natl Acad. Sci. USA 114, 4066–4071 (2017).

  13. 13.

    Israelachvili, J. N. Intermolecular and Surface Forces, 3rd edn (Academic, 2011).

  14. 14.

    de Gennes, P.-G. Scaling Concepts in Polymer physics (Cornell Univ. Press, 1979)..

  15. 15.

    Stevens, M. J., Berezney, J. P. & Saleh, O. A. The effect of chain stiffness and salt on the elastic response of a polyelectrolyte. J. Chem. Phys. 149, 163328 (2018).

  16. 16.

    Berezney, J. P. & Saleh, O. A. Electrostatic effects on the conformation and elasticity of hyaluronic acid, a moderately flexible polyelectrolyte. Macromolecules 50, 1085–1089 (2017).

  17. 17.

    Sassi, A. S., Assenza, S. & De Los Rios, P. Shape of a stretched polymer. Phys. Rev. Lett. 119, 037801 (2017).

  18. 18.

    Rubinstein, M. & Colby, R. H. Polymer Physics (Oxford Univ. Press, 2003).

  19. 19.

    Jung, J. M., Savin, G., Pouzot, M., Schmitt, C. & Mezzenga, R. Structure of heat-induced beta-lactoglobulin aggregates and their complexes with sodium-dodecyl sulfate. Biomacromolecules 9, 2477–2486 (2008).

  20. 20.

    Ortiz-Tafoya, M. C., Rolland-Sabate, A., Garnier, C., Valadez-Garcia, J. & Tecante, A. Thermal, conformational and rheological properties of kappa-carrageenan-sodium stearoyl lactylate gels and solutions. Carbohydr. Polym. 193, 289–297 (2018).

  21. 21.

    Hofmann, H. et al. Polymer scaling laws of unfolded and intrinsically disordered proteins quantified with single-molecule spectroscopy. Proc. Natl Acad. Sci. USA 109, 16155–16160 (2012).

  22. 22.

    Kellner, R. et al. Single-molecule spectroscopy reveals chaperone-mediated expansion of substrate protein. Proc. Natl Acad. Sci. USA 111, 13355–13360 (2014).

  23. 23.

    Clisby, N. Accurate estimate of the critical exponent nu for self-avoiding walks via a fast implementation of the pivot algorithm. Phys. Rev. Lett. 104, 055702 (2010).

  24. 24.

    Le Guillou, J. C. & Zinn-Justin, J. Critical exponents from field theory. Phys. Rev. B 21, 3976–3998 (1980).

  25. 25.

    Kohn, J. E. et al. Random-coil behavior and the dimensions of chemically unfolded proteins. Proc. Natl Acad. Sci. USA 101, 12491–12496 (2004).

  26. 26.

    Valle, F., Favre, M., De Los Rios, P., Rosa, A. & Dietler, G. Scaling exponents and probability distributions of DNA end-to-end distance. Phys. Rev. Lett. 95, 158105 (2005).

  27. 27.

    Dahesh, M., Banc, A., Duri, A., Morel, M. H. & Ramos, L. Polymeric assembly of gluten proteins in an aqueous ethanol solvent. J. Phys. Chem. B 118, 11065–11076 (2014).

  28. 28.

    Dalheim, M. O., Arnfinnsdottir, N. B., Widmalm, G. & Christensen, B. E. The size and shape of three water-soluble, non-ionic polysaccharides produced by lactic acid bacteria: a comparative study. Carbohydr. Polym. 142, 91–97 (2016).

  29. 29.

    Lara, C., Usov, I., Adamcik, J. & Mezzenga, R. Sub-persistence-length complex scaling behavior in lysozyme amyloid fibrils. Phys. Rev. Lett. 107, 238101 (2011).

  30. 30.

    Usov, I., Adamcik, J. & Mezzenga, R. Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils. ACS Nano 7, 10465–10474 (2013).

  31. 31.

    Schuler, B., Soranno, A., Hofmann, H. & Nettels, D. Single-molecule FRET spectroscopy and the polymer physics of unfolded and intrinsically disordered proteins. Annu. Rev. Biophys. 45, 207–231 (2016).

  32. 32.

    Gittes, F., Mickey, B., Nettleton, J. & Howard, J. Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. J. Cell Biol. 120, 923–934 (1993).

  33. 33.

    Adamcik, J. et al. Understanding amyloid aggregation by statistical analysis of atomic force microscopy images. Nat. Nanotechnol. 5, 423–428 (2010).

  34. 34.

    Loveday, S. M. & Gunning, A. P. Nanomechanics of pectin-linked beta-lactoglobulin nanofibril bundles. Biomacromolecules 19, 2834–2840 (2018).

  35. 35.

    Teckentrup, J. et al. Comparative analysis of different xanthan samples by atomic force microscopy. J. Biotechnol. 257, 2–8 (2017).

  36. 36.

    Jiang, X., Ryoki, A. & Terao, K. Dimensional and hydrodynamic properties of cellulose tris (alkylcarbamate)s in solution: side chain dependent conformation in tetrahydrofuran. Polymer 112, 152–158 (2017).

  37. 37.

    Ryoki, A., Kim, D., Kitamura, S. & Terao, K. Linear and cyclic amylose derivatives having brush like side groups in solution: amylose tris(n-octadecylcarbamate)s. Polymer 137, 13–21 (2018).

  38. 38.

    Terao, K. et al. Side-chain-dependent helical conformation of amylose alkylcarbamates: amylose tris(ethylcarbamate) and amylose tris(n-hexylcarbamate). J. Phys. Chem. B 116, 12714–12720 (2012).

  39. 39.

    Sano, Y. et al. Solution properties of amylose tris(n-butylcarbamate). Helical and global conformation in alcohols. Polymer 51, 4243–4248 (2010).

  40. 40.

    Schefer, L., Usov, I. & Mezzenga, R. Anomalous stiffening and ion-induced coil–helix transition of carrageenans under monovalent salt conditions. Biomacromolecules 16, 985–991 (2015).

  41. 41.

    Schefer, L., Adamcik, J. & Mezzenga, R. Unravelling secondary structure changes on individual anionic polysaccharide chains by atomic force microscopy. Angew. Chem. 53, 5376–5379 (2014).

  42. 42.

    Tirrell, M. V., Granick, S. & Muthukumar, M. Preface: special topic on chemical physics of charged macromolecules. J. Chem. Phys. 149, 163001 (2018).

  43. 43.

    Odijk, T. Polyelectrolytes near the rod limit. J. Polym. Sci. Polym. Phys. Ed. 15, 477–483 (1977).

  44. 44.

    Skolnick, J. & Fixman, M. Electrostatic persistence length of a wormlike polyelectrolyte. Macromolecules 10, 944–948 (1977).

  45. 45.

    Barrat, J. L. & Joanny, J. F. Persistence length of polyelectrolyte chains. Europhys. Lett. 24, 333–338 (1993).

  46. 46.

    Caliskan, G. et al. Persistence length changes dramatically as RNA folds. Phys. Rev. Lett. 95, 268303 (2005).

  47. 47.

    Savelyev, A. Do monovalent mobile ions affect DNA’s flexibility at high salt content? Phys. Chem. Chem. Phys. 14, 2250–2254 (2012).

  48. 48.

    Saleh, O. A., McIntosh, D. B., Pincus, P. & Ribeck, N. Nonlinear low-force elasticity of single-stranded DNA molecules. Phys. Rev. Lett. 102, 068301 (2009).

  49. 49.

    Sim, A. Y., Lipfert, J., Herschlag, D. & Doniach, S. Salt dependence of the radius of gyration and flexibility of single-stranded DNA in solution probed by small-angle x-ray scattering. Phys. Rev. E 86, 021901 (2012).

  50. 50.

    Micka, U. & Kremer, K. Persistence length of the Debye–Hückel model of weakly charged flexible polyelectrolyte chains. Phys. Rev. E 54, 2653–2662 (1996).

  51. 51.

    Manning, G. S. Limiting laws and counterion condensation in polyelectrolyte solutions. I. Colligative properties. J. Chem. Phys. 51, 924–933 (1969).

  52. 52.

    Dobrynin, A. & Rubinstein, M. Theory of polyelectrolytes in solutions and at surfaces. Prog. Polym. Sci. 30, 1049–1118 (2005).

  53. 53.

    Irani, A. H., Owen, J. L., Mercadante, D. & Williams, M. A. Molecular dynamics simulations illuminate the role of counterion condensation in the electrophoretic transport of homogalacturonans. Biomacromolecules 18, 505–516 (2017).

  54. 54.

    Netz, R. R. & Orland, H. Variational charge renormalization in charged systems. Eur. Phys. J. E 11, 301–311 (2003).

  55. 55.

    Marko, J. F. & Siggia, E. D. Stretching DNA. Macromolecules 28, 8759–8770 (1995).

  56. 56.

    Bustamante, C., Bryant, Z. & Smith, S. B. Ten years of tension: single-molecule DNA mechanics. Nature 421, 423–427 (2003).

  57. 57.

    Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J. M. & Gaub, H. E. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276, 1109–1112 (1997).

  58. 58.

    Rief, M., Oesterhelt, F., Heymann, B. & Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 275, 1295–1297 (1997).

  59. 59.

    Camunas-Soler, J., Ribezzi-Crivellari, M. & Ritort, F. Elastic properties of nucleic acids by single-molecule force spectroscopy. Annu. Rev. Biophys. 45, 65–84 (2016).

  60. 60.

    Hughes, M. L. & Dougan, L. The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding. Rep. Prog. Phys. Phys. Soc. 79, 076601 (2016).

  61. 61.

    Lakshminarayanan, A., Richard, M. & Davis, B. G. Studying glycobiology at the single-molecule level. Nat. Rev. Chem. 2, 148–159 (2018).

  62. 62.

    Naranjo, T. et al. Dynamics of individual molecular shuttles under mechanical force. Nat. Commun. 9, 4512 (2018).

  63. 63.

    Camunas-Soler, J., Alemany, A. & Ritort, F. Experimental measurement of binding energy, selectivity, and allostery using fluctuation theorems. Science 355, 412–415 (2017).

  64. 64.

    Gunning, A. P. & Morris, V. J. Getting the feel of food structure with atomic force microscopy. Food Hydrocoll. 78, 62–76 (2018).

  65. 65.

    Qian, L., Bao, Y., Duan, W. & Cui, S. Effects of water content of the mixed solvent on the single-molecule mechanics of amylose. ACS Macro Lett. 7, 672–676 (2018).

  66. 66.

    Marszalek, P. E., Li, H., Oberhauser, A. F. & Fernandez, J. M. Chair–boat transitions in single polysaccharide molecules observed with force-ramp AFM. Proc. Natl Acad. Sci. USA 99, 4278–4283 (2002).

  67. 67.

    Marszalek, P. E., Oberhauser, A. F., Pang, Y. P. & Fernandez, J. M. Polysaccharide elasticity governed by chair–boat transitions of the glucopyranose ring. Nature 396, 661–664 (1998).

  68. 68.

    Lara, Cc, Adamcik, J., Jordens, S. & Mezzenga, R. General self-assembly mechanism converting hydrolyzed globular proteins into giant multistranded amyloid ribbons. Biomacromolecules 12, 1868–1875 (2011).

  69. 69.

    Assenza, S., Adamcik, J., Mezzenga, R. & De Los Rios, P. Universal behavior in the mesoscale properties of amyloid fibrils. Phys. Rev. Lett. 113, 268103 (2014).

  70. 70.

    Goldsbury, C. S. et al. Polymorphic fibrillar assembly of human amylin. J. Struct. Biol. 119, 17–27 (1997).

  71. 71.

    Moffat, J., Morris, V. J., Al-Assaf, S. & Gunning, A. P. Visualisation of xanthan conformation by atomic force microscopy. Carbohydr. Polym. 148, 380–389 (2016).

  72. 72.

    Koziol, A., Cybulska, J., Pieczywek, P. M. & Zdunek, A. Evaluation of structure and assembly of xyloglucan from tamarind seed (Tamarindus indica L.) with atomic force microscopy. Food Biophys. 10, 396–402 (2015).

  73. 73.

    Xiao, M. et al. Investigation on curdlan dissociation by heating in water. Food Hydrocoll. 70, 57–64 (2017).

  74. 74.

    Schefer, L., Adamcik, J., Diener, M. & Mezzenga, R. Supramolecular chiral self-assembly and supercoiling behavior of carrageenans at varying salt conditions. Nanoscale 7, 16182–16188 (2015).

  75. 75.

    Mezzenga, R. & Fischer, P. The self-assembly, aggregation and phase transitions of food protein systems in one, two and three dimensions. Rep. Prog. Phys. Phys. Soc. 76, 046601 (2013).

  76. 76.

    Fusco, D. & Charbonneau, P. Soft matter perspective on protein crystal assembly. Colloids Surf. B 137, 22–31 (2016).

  77. 77.

    Platten, F., Valadez-Perez, N. E., Castaneda-Priego, R. & Egelhaaf, S. U. Extended law of corresponding states for protein solutions. J. Chem. Phys. 142, 174905 (2015).

  78. 78.

    Platten, F., Hansen, J., Wagner, D. & Egelhaaf, S. U. Second virial coefficient as determined from protein phase behavior. J. Phys. Chem. Lett. 7, 4008–4014 (2016).

  79. 79.

    Baxter, R. J. Percus–yevick equation for hard spheres with surface adhesion. J. Chem. Phys. 49, 2770–2774 (1968).

  80. 80.

    Asakura, S. & Oosawa, F. Interaction between particles suspended in solutions of macromolecules. J. Polym. Sci. 33, 183–192 (1958).

  81. 81.

    Asakura, S. & Oosawa, F. On Interaction between two bodies immersed in a solution of macromolecules. J. Chem. Phys. 22, 1255–1256 (1954).

  82. 82.

    Woldeyes, M. A., Calero-Rubio, C., Furst, E. M. & Roberts, C. J. Predicting protein interactions of concentrated globular protein solutions using colloidal models. J. Phys. Chem. B 121, 4756–4767 (2017).

  83. 83.

    Braun, M. K. et al. Strong isotope effects on effective interactions and phase behavior in protein solutions in the presence of multivalent ions. J. Phys. Chem. B 121, 1731–1739 (2017).

  84. 84.

    Bucciarelli, S. et al. Extended law of corresponding states applied to solvent isotope effect on a globular protein. J. Phys. Chem. Lett. 7, 1610–1615 (2016).

  85. 85.

    Hansen, J., Platten, F., Wagner, D. & Egelhaaf, S. U. Tuning protein–protein interactions using cosolvents: specific effects of ionic and non-ionic additives on protein phase behavior. Phys. Chem. Chem. Phys. 18, 10270–10280 (2016).

  86. 86.

    Noro, M. G. & Frenkel, D. Extended corresponding-states behavior for particles with variable range attractions. J. Chem. Phys. 113, 2941–2944 (2000).

  87. 87.

    Bárcenas, M., Castellanos, V., Reyes, Y., Odriozola, G. & Orea, P. Phase behaviour of short range triangle well fluids: a comparison with lysozyme suspensions. J. Mol. Liq. 225, 723–729 (2017).

  88. 88.

    Sciortino, F. & Zaccarelli, E. Reversible gels of patchy particles. Curr. Opin. Solid State Mater. Sci. 15, 246–253 (2011).

  89. 89.

    Liu, H., Kumar, S. K. & Sciortino, F. Vapor-liquid coexistence of patchy models: relevance to protein phase behavior. J. Chem. Phys. 127, 084902 (2007).

  90. 90.

    Gogelein, C. et al. A simple patchy colloid model for the phase behavior of lysozyme dispersions. J. Chem. Phys. 129, 085102 (2008).

  91. 91.

    Foffi, G. & Sciortino, F. On the possibility of extending the Noro–Frenkel generalized law of correspondent states to nonisotropic patchy interactions. J. Phys. Chem. B 111, 9702–9705 (2007).

  92. 92.

    Boire, A., Sanchez, C., Morel, M. H., Lettinga, M. P. & Menut, P. Dynamics of liquid–liquid phase separation of wheat gliadins. Sci. Rep. 8, 14441 (2018).

  93. 93.

    Grimaldo, M. et al. Salt-induced universal slowing down of the short-time self-diffusion of a globular protein in aqueous solution. J. Phys. Chem. Lett. 6, 2577–2582 (2015).

  94. 94.

    Bucciarelli, S. et al. Dramatic influence of patchy attractions on short-time protein diffusion under crowded conditions. Sci. Adv. 2, e1601432 (2016).

  95. 95.

    Cai, J. & Sweeney, A. M. The proof is in the pidan: generalizing proteins as patchy particles. ACS Cent. Sci. 4, 840–853 (2018).

  96. 96.

    Cai, J., Townsend, J. P., Dodson, T. C., Heiney, P. A. & Sweeney, A. M. Eye patches: protein assembly of index-gradient squid lenses. Science 357, 564–569 (2017).

  97. 97.

    Fries, M. R. et al. Multivalent-ion-activated protein adsorption reflecting bulk reentrant behavior. Phys. Rev. Lett. 119, 228001 (2017).

  98. 98.

    Roosen-Runge, F., Zhang, F., Schreiber, F. & Roth, R. Ion-activated attractive patches as a mechanism for controlled protein interactions. Sci. Rep. 4, 7016 (2014).

  99. 99.

    Stopper, D., Hirschmann, F., Oettel, M. & Roth, R. Bulk structural information from density functionals for patchy particles. J. Chem. Phys. 149, 224503 (2018).

  100. 100.

    Yigit, C., Heyda, J. & Dzubiella, J. Charged patchy particle models in explicit salt: ion distributions, electrostatic potentials, and effective interactions. J. Chem. Phys. 143, 064904 (2015).

  101. 101.

    Blanco, M. A. & Shen, V. K. Effect of the surface charge distribution on the fluid phase behavior of charged colloids and proteins. J. Chem. Phys. 145, 155102 (2016).

  102. 102.

    Garcia, N. A., Gnan, N. & Zaccarelli, E. Effective potentials induced by self-assembly of patchy particles. Soft Matter 13, 6051–6058 (2017).

  103. 103.

    Newton, A. C., Kools, R., Swenson, D. W. H. & Bolhuis, P. G. The opposing effects of isotropic and anisotropic attraction on association kinetics of proteins and colloids. J. Chem. Phys. 147, 155101 (2017).

  104. 104.

    Bleibel, J. et al. Two time scales for self and collective diffusion near the critical point in a simple patchy model for proteins with floating bonds. Soft Matter 14, 8006–8016 (2018).

  105. 105.

    Jansens, K. J. A. et al. Rational design of amyloid-like fibrillary structures for tailoring food protein techno-functionality and their potential health implications. Compr. Rev. Food Sci. Food Saf. 18, 84–105 (2019).

  106. 106.

    Boire, A. et al. Soft matter approaches for controlling food protein interactions and assembly. Annu. Rev. Food Sci. Technol. (2019).

  107. 107.

    McManus, J. J., Charbonneau, P., Zaccarelli, E. & Asherie, N. The physics of protein self-assembly. Curr. Opin. Colloid Interface Sci. 22, 73–79 (2016).

  108. 108.

    Sciortino, F., Mossa, S., Zaccarelli, E. & Tartaglia, P. Equilibrium cluster phases and low-density arrested disordered states: the role of short-range attraction and long-range repulsion. Phys. Rev. Lett. 93, 055701 (2004).

  109. 109.

    Stradner, A. et al. Equilibrium cluster formation in concentrated protein solutions and colloids. Nature 432, 492–495 (2004).

  110. 110.

    Jachimska, B., Wasilewska, M. & Adamczyk, Z. Characterization of globular protein solutions by dynamic light scattering, electrophoretic mobility, and viscosity measurements. Langmuir 24, 6866–6872 (2008).

  111. 111.

    Ianeselli, L. et al. Protein-protein interactions in ovalbumin solutions studied by small-angle scattering: effect of ionic strength and the chemical nature of cations. J. Phys. Chem. B 114, 3776–3783 (2010).

  112. 112.

    Shukla, A. et al. Absence of equilibrium cluster phase in concentrated lysozyme solutions. Proc. Natl Acad. Sci. USA 105, 5075–5080 (2008).

  113. 113.

    Liu, Y., Fratini, E., Baglioni, P., Chen, W. R. & Chen, S. H. Effective long-range attraction between protein molecules in solutions studied by small angle neutron scattering. Phys. Rev. Lett. 95, 118102 (2005).

  114. 114.

    StradnerA.., Cardinaux FEgelhaaf, S. U. & Schurtenberger, P. Do equilibrium clusters exist in concentrated lysozyme solutions? Proc. Natl Acad. Sci. USA 105, E75; author reply E76, (2008).

  115. 115.

    Cardinaux, F. et al. Cluster-driven dynamical arrest in concentrated lysozyme solutions. J. Phys. Chem. B 115, 7227–7237 (2011).

  116. 116.

    Bergman, M. J., Garting, T., Schurtenberger, P. & Stradner, A. Experimental evidence for a cluster glass transition in concentrated lysozyme solutions. J. Phys. Chem. B 123, 2432–2438 (2019).

  117. 117.

    Riest, J., Nagele, G., Liu, Y., Wagner, N. J. & Godfrin, P. D. Short-time dynamics of lysozyme solutions with competing short-range attraction and long-range repulsion: experiment and theory. J. Chem. Phys. 148, 065101 (2018).

  118. 118.

    Kundu, S., Aswal, V. K. & Kohlbrecher, J. Synergistic effect of temperature, protein and salt concentration on structures and interactions among lysozyme proteins. Chem. Phys. Lett. 657, 90–94 (2016).

  119. 119.

    Skar-Gislinge, N. et al. A colloid approach to self-assembling antibodies. Preprint at (2018).

  120. 120.

    Vega, C. & Mercadé-Prieto, R. Culinary biophysics: on the nature of the 6X°C egg. Food Biophys. 6, 152–159 (2011).

  121. 121.

    Lepetit, J. A theoretical approach of the relationships between collagen content, collagen cross-links and meat tenderness. Meat Sci. 76, 147–159 (2007).

  122. 122.

    Miocinovic, J. et al. Rheological and textural properties of goat and cow milk set type yoghurts. Int. Dairy J. 58, 43–45 (2016).

  123. 123.

    Baussay, K., Bon, C. L., Nicolai, T., Durand, D. & Busnel, J.-P. Influence of the ionic strength on the heat-induced aggregation of the globular protein β-lactoglobulin at pH 7. Int. J. Biol. Macromol. 34, 21–28 (2004).

  124. 124.

    Pouzot, M., Nicolai, T., Durand, D. & Benyahia, L. Structure factor and elasticity of a heat-set globular protein gel. Macromolecules 37, 614–620 (2004).

  125. 125.

    Nieuwland, M., Bouwman, W. G., Pouvreau, L., Martin, A. H. & de Jongh, H. H. J. Relating water holding of ovalbumin gels to aggregate structure. Food Hydrocoll. 52, 87–94 (2016).

  126. 126.

    Chen, N., Zhao, M., Chassenieux, C. & Nicolai, T. Structure of self-assembled native soy globulin in aqueous solution as a function of the concentration and the pH. Food Hydrocoll. 56, 417–424 (2016).

  127. 127.

    Banc, A. et al. Small angle neutron scattering contrast variation reveals heterogeneities of interactions in protein gels. Soft Matter 12, 5340–5352 (2016).

  128. 128.

    Dahesh, M., Banc, A., Duri, A., Morel, M.-H. & Ramos, L. Spontaneous gelation of wheat gluten proteins in a food grade solvent. Food Hydrocoll. 52, 1–10 (2016).

  129. 129.

    Ahmed, K. F., Aschi, A. & Nicolai, T. Formation and characterization of chitosan–protein particles with fractal whey protein aggregates. Colloids Surf. B 169, 257–264 (2018).

  130. 130.

    Doi, M. & Onuki, A. Dynamic coupling between stress and composition in polymer solutions and blends. J. Phys. II 2, 1631–1656 (1992).

  131. 131.

    Kantor, Y. & Webman, I. Elastic properties of random percolating systems. Phys. Rev. Lett. 52, 1891–1894 (1984).

  132. 132.

    Rafe, A. & Razavi, S. M. A. Scaling law, fractal analysis and rheological characteristics of physical gels cross-linked with sodium trimetaphosphate. Food Hydrocoll. 62, 58–65 (2017).

  133. 133.

    MacKintosh, F. C., Kas, J. & Janmey, P. A. Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995).

  134. 134.

    Cao, Y., Bolisetty, S., Adamcik, J. & Mezzenga, R. Elasticity in physically cross-linked amyloid fibril networks. Phys. Rev. Lett. 120, 158103 (2018).

  135. 135.

    Salentinig, S., Phan, S., Khan, J., Hawley, A. & Boyd, B. J. Formation of highly organized nanostructures during the digestion of milk. ACS nano 7, 10904–10911 (2013).

  136. 136.

    Salentinig, S., Phan, S., Hawley, A. & Boyd, B. J. Self-assembly structure formation during the digestion of human breast milk. Angew. Chem. 54, 1600–1603 (2015).

  137. 137.

    Salentinig, S., Amenitsch, H. & Yaghmur, A. In situ monitoring of nanostructure formation during the digestion of mayonnaise. ACS omega 2, 1441–1446 (2017).

  138. 138.

    Leibler, L. Theory of microphase separation in block copolymers. Macromolecules 13, 1602–1617 (1980).

  139. 139.

    Mezzenga, R. Physics of self-assembly of lyotropic liquid crystals. (2012).

  140. 140.

    Qiu, H. & Caffrey, M. The phase diagram of the monoolein/water system: metastability and equilibrium aspects. Biomaterials 21, 223–234 (2000).

  141. 141.

    Mezzenga, R. et al. Shear rheology of lyotropic liquid crystals: a case study. Langmuir 21, 3322–3333 (2005).

  142. 142.

    Barauskas, J. & Landh, T. Phase Behavior of the phytantriol/water system. Langmuir 19, 9562–9565 (2003).

  143. 143.

    Israelachvili, J. N., Mitchell, D. J. & Ninham, B. W. Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J. Chem. Soc. Faraday Trans. 2 72, 1525 (1976).

  144. 144.

    Lee, W. B., Mezzenga, R. & Fredrickson, G. H. Anomalous phase sequences in lyotropic liquid crystals. Phys. Rev. Lett. 99, 187801 (2007).

  145. 145.

    Müller, M. & Schick, M. Calculation of the phase behavior of lipids. Phys. Rev. E 57, 6973–6978 (1998).

  146. 146.

    Templer, R. H., Seddon, J. M., Duesing, P. M., Winter, R. & Erbes, J. Modeling the phase behavior of the inverse hexagonal and inverse bicontinuous cubic phases in 2:1 fatty acid/phosphatidylcholine mixtures. J. Phys. Chem. B 102, 7262–7271 (1998).

  147. 147.

    Schwarz, U. S. & Gompper, G. Bending frustration of lipid−water mesophases based on cubic minimal surfaces. Langmuir 17, 2084–2096 (2001).

  148. 148.

    Oka, T., Ohta, N. & Hyde, S. Polar–nonpolar interfaces of inverse bicontinuous cubic phases in phytantriol/water system are parallel to triply periodic minimal surfaces. Langmuir 34, 15462–15469 (2018).

  149. 149.

    Barriga, H. M. G., Holme, M. N. & Stevens, M. M. Cubosomes: the next generation of smart lipid nanoparticles? Angew. Chem. (2018).

  150. 150.

    Yaghmur, A., de Campo, L., Sagalowicz, L., Leser, M. E. & Glatter, O. Control of the internal structure of MLO-based isasomes by the addition of diglycerol monooleate and soybean phosphatidylcholine. Langmuir 22, 9919–9927 (2006).

  151. 151.

    Negrini, R. & Mezzenga, R. Diffusion, molecular separation, and drug delivery from lipid mesophases with tunable water channels. Langmuir 28, 16455–16462 (2012).

  152. 152.

    Tyler, A. I. et al. Electrostatic swelling of bicontinuous cubic lipid phases. Soft Matter 11, 3279–3286 (2015).

  153. 153.

    Leung, S. S. W. & Leal, C. The stabilization of primitive bicontinuous cubic phases with tunable swelling over a wide composition range. Soft Matter. (2018).

  154. 154.

    Brasnett, C., Longstaff, G., Compton, L. & Seddon, A. Effects of cations on the behaviour of lipid cubic phases. Sci. Rep. 7, 8229 (2017).

  155. 155.

    Negrini, R. & Mezzenga, R. pH-responsive lyotropic liquid crystals for controlled drug delivery. Langmuir 27, 5296–5303 (2011).

  156. 156.

    Barriga, H. M. et al. Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales. Soft Matter 11, 600–607 (2015).

  157. 157.

    Fong, W.-K. et al. Dynamic formation of nanostructured particles from vesicles via invertase hydrolysis for on-demand delivery. RSC Adv. 7, 4368–4377 (2017).

  158. 158.

    Fong, W. K. et al. Generation of geometrically ordered lipid-based liquid-crystalline nanoparticles using biologically relevant enzymatic processing. Langmuir 30, 5373–5377 (2014).

  159. 159.

    Salentinig, S., Sagalowicz, L., Leser, M. E., Tedeschi, C. & Glatter, O. Transitions in the internal structure of lipid droplets during fat digestion. Soft Matter 7, 650–661 (2011).

  160. 160.

    Sadeghpour, A., Rappolt, M., Misra, S. & Kulkarni, C. V. Bile salts caught in the act: from emulsification to nanostructural reorganization of lipid self-assemblies. Langmuir 34, 13626–13637 (2018).

  161. 161.

    Clulow, A. J., Salim, M., Hawley, A. & Boyd, B. J. A closer look at the behaviour of milk lipids during digestion. Chem. Phys. lipids 211, 107–116 (2018).

  162. 162.

    McClements, D. J. Encapsulation, protection, and release of hydrophilic active components: potential and limitations of colloidal delivery systems. Adv. Colloid Interface Sci. 219, 27–53 (2015).

  163. 163.

    Sagalowicz, L. et al. Lipid self-assembled structures for reactivity control in food. Phil. Trans. A 374, (2016).

  164. 164.

    Martiel, I. et al. Oil and drug control the release rate from lyotropic liquid crystals. J. Control. Release 204, 78–84 (2015).

  165. 165.

    Clogston, J. & Caffrey, M. Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins and nucleic acids. J. Control. Release 107, 97–111 (2005).

  166. 166.

    Meikle, T. G. et al. Predicting the release profile of small molecules from within the ordered nanostructured lipidic bicontinuous cubic phase using translational diffusion coefficients determined by PFG-NMR. Nanoscale 9, 2471–2478 (2017).

  167. 167.

    Fong, W. K., Hanley, T. & Boyd, B. J. Stimuli responsive liquid crystals provide ‘on-demand' drug delivery in vitro and in vivo. J. Control. Release 135, 218–226 (2009).

  168. 168.

    Assenza, S. & Mezzenga, R. Curvature and bottlenecks control molecular transport in inverse bicontinuous cubic phases. J. Chem. Phys. 148, 054902 (2018).

  169. 169.

    Kim, J. et al. Ultrafast hydration dynamics in the lipidic cubic phase: discrete water structures in nanochannels. J. Phys. Chem. B 110, 21994–22000 (2006).

  170. 170.

    Mezzenga, R. Equilibrium and non-equilibrium structures in complex food systems. Food Hydrocoll. 21, 674–682 (2007).

  171. 171.

    Bhat, S., Tuinier, R. & Schurtenberger, P. Spinodal decomposition in a food colloid–biopolymer mixture: evidence for a linear regime. J. Phys. Condens Matter 18, L339–L346 (2006).

  172. 172.

    Mahmoudi, N. & Stradner, A. Structural arrest and dynamic localization in biocolloidal gels. Soft Matter 13, 4629–4635 (2017).

  173. 173.

    Bolisetty, S. & Mezzenga, R. Amyloid-carbon hybrid membranes for universal water purification. Nat. Nanotechnol. 11, 365–371 (2016).

  174. 174.

    Shen, Y. et al. Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron. Nat. Nanotechnol. 12, 642–647 (2017).

  175. 175.

    Nagy, K. et al. Vitamin E and vitamin E acetate absorption from self-assembly systems under pancreas insufficiency conditions. Chimia 68, 129–134 (2014).

  176. 176.

    Springmann, M. et al. Options for keeping the food system within environmental limits. Nature 562, 519–525 (2018).

  177. 177.

    Matsuyama, A. & Tanaka, F. Theory of solvation-induced reentrant phase separation in polymer solutions. Phys. Rev. Lett. 65, 341–344 (1990).

  178. 178.

    Takahashi, M., Shimazaki, M. & Yamamoto, J. Thermoreversible gelation and phase separation in aqueous methyl cellulose solutions. J. Polym. Sci. B 39, 91–100 (2001).

  179. 179.

    Rwei, S.-P. & Lyu, M.-S. 3-D phase diagram of HPC/H2O/H3PO4 tertiary system. Cellulose 19, 1065–1074 (2012).

  180. 180.

    Brangwynne, C. P., Tompa, P. & Pappu, R. V. Polymer physics of intracellular phase transitions. Nat. Phys. 11, 899–904 (2015).

  181. 181.

    Pak, C. W. et al. Sequence determinants of intracellular phase separation by complex coacervation of a disordered protein. Mol. Cell 63, 72–85 (2016).

  182. 182.

    Wu, X. et al. Gelation of β-lactoglobulin and its fibrils in the presence of transglutaminase. Food Hydrocoll. 52, 942–951 (2016).

  183. 183.

    Brownlow, S. et al. Bovine ß-lactoglobulin at 1.8 Å resolution — still an enigmatic lipocalin. Structure 5, 481–495 (1997).

  184. 184.

    Weiss, M. S., Palm, G. J. & Hilgenfeld, R. Crystallization, structure solution and refinement of hen egg-white lysozyme at pH 8.0 in the presence of MPD. Acta Crystallogr. D. 56, 952–958 (2000).

  185. 185.

    Jo, S., Vargyas, M., Vasko-Szedlar, J., Roux, B. & Im, W. PBEQ-solver for online visualization of electrostatic potential of biomolecules. Nucleic Acids Res. 36, W270–W275 (2008).

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The authors are indebted to W. K. Fong and M. Usuelli for discussions and thank A. Diego-González for producing the mayonnaise sample reported in Fig. 1a.

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Correspondence to Raffaele Mezzenga.

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Loss of secondary, tertiary and/or quaternary structure of a protein owing to temperature or chemical stress, for example.

Amyloid fibrils

Protein and peptide-based fibrous aggregates with a characteristic cross-ß secondary structure.

Thermal blob

The portion of chain length whose total interaction energy is of the order of kBT.


When peptide chains are fragmented into shorter subunits by chemical, enzymatic or thermal stimuli.

Hamaker constant

A quantity with the units of energy characterizing the van der Waals interactions between colloids.

Second virial coefficient

A quantity with units of volume describing the net two-body interactions between two particles; positive and negative values indicate net repulsion and attraction, respectively.

Association kinetics

Dynamic features of binding between particles, usually characterized by suitable rate constants.

Isoelectric point

Value of pH for which partial protonation induces a net zero charge in a molecule hosting several positively charged and negatively charged groups.

Storage modulus

Parameter with the units of pressure quantifying the elastic response of a viscoelastic material to an external stress.

Block copolymers

Macromolecules obtained by covalently joining two polymers with different physico-chemical properties by one end.

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