Physical biology of the cancer cell glycocalyx

Abstract

The glycocalyx coating the outside of most cells is a polymer meshwork comprising proteins and complex sugar chains called glycans. From a physical perspective, the glycocalyx has long been considered a simple ‘slime’ that protects cells from mechanical disruption or against pathogen interactions, but the great complexity of the structure argues for the evolution of more advanced functionality: the glycocalyx serves as the complex physical environment within which cell-surface receptors reside and operate. Recent studies have demonstrated that the glycocalyx can exert thermodynamic and kinetic control over cell signalling by serving as the local medium within which receptors diffuse, assemble and function. The composition and structure of the glycocalyx change markedly with changes in cell state, including transformation. Notably, cancer-specific changes fuel the synthesis of monomeric building blocks and machinery for production of long-chain polymers that alter the physical and chemical structure of the glycocalyx. In this Review, we discuss these changes and their physical consequences on receptor function and emergent cell behaviours.

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Fig. 1: Overview of large polymers on the cancer cell surface.
Fig. 2: Glycocalyx architecture and communication interface on the cell surface.
Fig. 3: Physical aspects of polymers.
Fig. 4: Cancer cell metabolism is rewired to produce large polymers in the glycocalyx.
Fig. 5: Donnan equilibrium between the glycocalyx and surrounding fluid.
Fig. 6: Excluded volumes depict crowding in the glycocalyx.
Fig. 7: Tethered ligand binding.

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Acknowledgements

This work was supported by the National Institute of Health New Innovator DP2 GM229133 (M.J.P) and the Center on the Physics of Cancer Metabolism through award no. 1U54CA210184-01 from the National Cancer Institute (M.J.P). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Kuo, J.CH., Gandhi, J.G., Zia, R.N. et al. Physical biology of the cancer cell glycocalyx. Nature Phys 14, 658–669 (2018). https://doi.org/10.1038/s41567-018-0186-9

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