Theoretical model of membrane protrusions driven by curved active proteins

Front Mol Biosci. 2023 May 9:10:1153420. doi: 10.3389/fmolb.2023.1153420. eCollection 2023.

Abstract

Eukaryotic cells intrinsically change their shape, by changing the composition of their membrane and by restructuring their underlying cytoskeleton. We present here further studies and extensions of a minimal physical model, describing a closed vesicle with mobile curved membrane protein complexes. The cytoskeletal forces describe the protrusive force due to actin polymerization which is recruited to the membrane by the curved protein complexes. We characterize the phase diagrams of this model, as function of the magnitude of the active forces, nearest-neighbor protein interactions and the proteins' spontaneous curvature. It was previously shown that this model can explain the formation of lamellipodia-like flat protrusions, and here we explore the regimes where the model can also give rise to filopodia-like tubular protrusions. We extend the simulation with curved components of both convex and concave species, where we find the formation of complex ruffled clusters, as well as internalized invaginations that resemble the process of endocytosis and macropinocytosis. We alter the force model representing the cytoskeleton to simulate the effects of bundled instead of branched structure, resulting in shapes which resemble filopodia.

Keywords: Monte-Carlo simulations; cell membrane; cell motility; closed vesicle shapes; curved inclusions; filopodia.

Grants and funding

NG is the incumbent of the Lee and William Abramowitz Professorial Chair of Biophysics, and acknowledges support by the Ben May Center for Theory and Computation, and the Israel Science Foundation (Grant No. 207/22). AI and SM were supported by the Slovenian Research Agency (ARRS) through the Grants Nos. J3-3066 and J2-4447 and Programme No. P2-0232. YK and SS was supported by grants from the JSPS (KAKENHI JP20H03252, JP20KK0341, and JP21H05047) and JST CREST (JPMJCR 1863) to SS and Takeda Science Foundation, a Grant-in-Aid for Challenging Exploratory Research (KAKENHI No. 20K20379), and JST CREST (JPMJCR 1863) to YK.