Theoretical model of membrane protrusions driven by curved active proteins

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.

Pathological and Therapeutic Significance of Tumor-Derived Extracellular Vesicles in Cancer Cell Migration and Metastasis

“…It was recently found that a high concentration of curved proteins may induce protrusive forces and sheet-like lamellipodia on highly curved surfaces in order to minimize membrane free energy [33,34]. Theoretical considerations show that the redistribution of membrane proteins and active forces are closely connected to the membrane shape [35].…”

Pre-organized landscape of T cell surface

“…Multimeric interactions between receptors can drive the formation of nanodomains in the plasma membrane ( 21 , 22 ). Topographical structures, such as protrusions, can also cause the segregation of receptors ( 23 – 25 ). The ability of membrane proteins to associate with cortical cytoskeleton may also affect the localization and clustering of receptors ( 24 , 26 , 27 ).…”

Forceful patterning: theoretical principles of mechanochemical pattern formation

“…For example, curvature‐mediated pattern formation plays a role in the formation of cellular protrusions, such as those involved in cell migration or myelination‐like coiling. There, proteins such as curved BAR proteins couple to membrane shape and interact with the actin cytoskeleton, producing dynamic patterns and protrusions on the cell surface (Simunovic et al , 2015; Carman & Dominguez, 2018; Gov, 2018; Wu et al , 2018; Begemann et al , 2019; Sadhu et al , 2021, 2023; Ravid et al , 2023).…”