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Stability Analysis of a Bulk–Surface Reaction Model for Membrane Protein Clustering

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Abstract

Protein aggregation on the plasma membrane (PM) is of critical importance to many cellular processes such as cell adhesion, endocytosis, fibrillar conformation, and vesicle transport. Lateral diffusion of protein aggregates or clusters on the surface of the PM plays an important role in governing their heterogeneous surface distribution. However, the stability behavior of the surface distribution of protein aggregates remains poorly understood. Therefore, understanding the spatial patterns that can emerge on the PM solely through protein–protein interaction, lateral diffusion, and feedback is an important step toward a complete description of the mechanisms behind protein clustering on the cell surface. In this work, we investigate the pattern formation of a reaction–diffusion model that describes the dynamics of a system of ligand–receptor complexes. The purely diffusive ligand in the cytosol can bind receptors in the PM and the resultant ligand–receptor complexes not only diffuse laterally but can also form clusters resulting in different oligomers. Finally, the largest oligomers recruit ligands from the cytosol using positive feedback. From a methodological viewpoint, we provide theoretical estimates for diffusion-driven instabilities of the protein aggregates based on the Turing mechanism. Our main result is a threshold phenomenon, in which a sufficiently high recruitment of ligands promotes the input of new monomeric components and consequently drives the formation of a single-patch spatially heterogeneous steady state.

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Acknowledgements

This work was supported by Air Force Office of Scientific Research (AFOSR) Multidisciplinary University Research Initiative (MURI) Grant FA9550-18-1-0051 to P. Rangamani. M. Holst was supported in part by NSF Awards DMS 1620366 and DMS 1345013. We also thank the Ph.D students Jennifer Fromm, Allen Leung, and Kiersten Scott from the Rangamani Lab for the comments and feedback.

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  1. L. M. Stolerman and M. Getz have contributed equally to this work.

Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, 92093-0411, USA

    Lucas M. Stolerman, Michael Getz, Stefan G. Llewellyn Smith & Padmini Rangamani

  2. Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, 92093-0213, USA

    Stefan G. Llewellyn Smith

  3. Department of Mathematics, University of California, San Diego, La Jolla, CA, 92093-0112, USA

    Michael Holst

  4. Department of Physics, University of California, San Diego, La Jolla, CA, 92093-0424, USA

    Michael Holst

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  1. Lucas M. Stolerman
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Stolerman, L.M., Getz, M., Smith, S.G.L. et al. Stability Analysis of a Bulk–Surface Reaction Model for Membrane Protein Clustering. Bull Math Biol 82, 30 (2020). https://doi.org/10.1007/s11538-020-00703-4

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