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Control of protein-based pattern formation via guiding cues

Nature Reviews Physics volume 4, pages 511–527 (2022)Cite this article

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Abstract

Proteins control many vital functions in living cells, such as cell growth and cell division. Reliable coordination of these functions requires the spatial and temporal organization of proteins inside cells, which encodes information about the cell’s geometry and the cell-cycle stage. The study of such protein patterns has long focused around formation in uniform environments. However, in recent years, it has become evident that spatial heterogeneities are essential for protein patterning, and various guiding cues in the cell or at the cell boundary can be exploited to reliably control protein pattern formation. We review how protein patterns are guided by cell size and shape, by other protein patterns that act as templates, and by the mechanical properties of the cell. The basic mechanisms of guided pattern formation are elucidated with reference to observations in various biological model organisms. We posit that understanding the controlled formation of protein patterns in cells will be an essential part of understanding information processing in living systems.

Key points

  • Cells rely on spatial and temporal protein distributions to maintain their viability and biological function.

  • Intracellular protein patterns are controlled, oriented and positioned by guiding cues that include cell size and shape, pre-existing protein patterns and the cell’s mechanical properties.

  • A combination of theoretical models with experimental observations has shed new light on the mechanisms of protein pattern formation in cells.

  • Further uncovering of mechanisms underlying pattern guidance is key to developing a fundamental understanding of living systems.

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Fig. 1: Reaction and transport processes involved in pattern formation.
Fig. 2: Size and shape as guiding cues.
Fig. 3: Principles of biochemical pattern guidance.
Fig. 4: Stress gradients result in flows.

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Acknowledgements

The authors thank C. Beta, S. Grill, L. Laan, S. Meindlhumer, B. Ramm, P. Rangamani, T. H. Tan and A. Vecchiarelli for critical reading of the manuscript and for their input, which helped to clarify several issues discussed in this Review, and A. Goychuk and F. Brauns for discussions. The authors apologize to those whose work could not be discussed through limits on space and references. The authors acknowledge financial support by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through TRR 174 (Project ID no. 269423233), through B02 projects within the Collaborative Research Center SFB 1032 (Project ID no. 201269156) and through the Excellence Cluster ORIGINS under Germany’s Excellence Strategy (EXC-2094-390783311). M.C.W. is supported by a DFG fellowship within the Graduate School of Quantitative Biosciences Munich. M.C.W. and T.B. are supported by the Joachim Herz Foundation.

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  1. Arnold Sommerfeld Center for Theoretical Physics (ASC) and Center for NanoScience (CeNS), Department of Physics, Ludwig-Maximilians-Universität München, Munich, Germany

    Tom Burkart, Manon C. Wigbers, Laeschkir Würthner & Erwin Frey

  2. Max Planck School Matter to Life, Munich, Germany

    Erwin Frey

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Glossary

Nucleoside triphosphate

(NTP). Nucleotide molecules with three phosphate groups, typically based on guanine (GTP), adenine (ATP) or cytosine (CTP), forming the main carriers of chemical energy in cells. Nucleoside diphosphate (NDP) instead has two phosphate groups.

NTPases

An NTPase is an enzyme that binds to NTP and hydrolyses it to NDP, thereby releasing energy.

Phosphorylation

Proteins can be phosphorylated by the addition of a phosphate group, as a means of storing chemical energy.

Dephosphorylation

Removal of a phosphate group from a protein, in order to release chemical energy.

Oligomers

An oligomer is a complex made up of a few proteins of the same type (homo-oligomer) or a different type (hetero-oligomer).

Cytoplasm

Heterogeneous material making up most of the volume of a cell (excluding the nucleus), consisting primarily of the cytosol and macromolecular organelles.

Molecular motors

Enzymes that use energy released by NTP hydrolysis to perform mechanical work, and that are generally associated with cytoskeletal filaments.

Microtubules

Protein filaments composed of tubulin, which form an integral part of the cytoskeleton. Microtubules exhibit a polarity, with the ends denoted as plus and minus ends.

Actin filaments

Also known as microfilaments, these are polar filaments of actin proteins, which form an integral part of the cytoskeleton. Their ends are denoted as plus and minus ends.

Actin cortex

Thin and dynamic network that acts as a scaffold that determines the cell’s shape and which is comprised of actin filaments, motor proteins and other associated proteins.

BAR domain

A curved protein domain that binds to curved membranes, named after three proteins that contain this domain: Bin, amphiphysin and Rvs.

α-Helix

Prevalent helical-like protein structure, which is highly stable owing to hydrogen bonds.

Control parameter

A parameter that alters the qualitative dynamics when it is changed, also referred to as a bifurcation parameter in nonlinear dynamics.

Mitosis

Stage of the cell cycle during which chromosomes are segregated into the two daughter cells.

Apoptosis

Cellular process leading to actively induced cell death.

Meiosis

A type of cell-division process that generates daughter cells that contain half as many chromosomes as the parent cell.

Chemotaxis

Directed locomotion of cells along chemical gradients.

Endocytosis

Cellular process that enables the uptake of biomolecules into the interior of the cell.

Animal–vegetal axis

Symmetry axis in oocytes, along which the developmental activity varies, separating the cell into two distinct poles.

Giant unilamellar vesicles

(GUVs). A GUV is an artificial spherical chamber bounded by a lipid bilayer that mimics the membrane of cells.

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Burkart, T., Wigbers, M.C., Würthner, L. et al. Control of protein-based pattern formation via guiding cues. Nat Rev Phys 4, 511–527 (2022). https://doi.org/10.1038/s42254-022-00461-3

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