Abstract

SummaryMacropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions form without any external solid support, as opposed to the process of particle uptake during phagocytosis. Here, by developing a computational framework that describes the coupling between the bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrated that the protrusive force localized to the edge of the patches can give rise to a self-enclosing cup structure, without further assumptions of local bending or contraction. Efficient uptake requires a balance among the patch size, magnitude of protrusive force, and cortical tension. Furthermore, our model exhibits cyclic cup formation, coexistence of multiple cups, and cup-splitting, indicating that these complex morphologies self-organize via a common mutually-dependent process of reaction-diffusion and membrane deformation.

Highlights

  • Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process (King and Kay, 2019), in which the extracellular fluid is taken up by internalization of micrometer-scale cup-shaped membrane ruffles (Figure 1A)

  • SUMMARY Macropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry

  • By developing a computational framework that describes the coupling between the bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrated that the protrusive force localized to the edge of the patches can give rise to a self-enclosing cup structure, without further assumptions of local bending or contraction

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Summary

Introduction

Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process (King and Kay, 2019), in which the extracellular fluid is taken up by internalization of micrometer-scale cup-shaped membrane ruffles (Figure 1A). In contrast to phagocytic cups, which extend along the extracellular particles (Herant et al, 2006; Richards and Endres, 2017) (e.g., other cells to be engulfed for phagocytes, and pathogens for immune cells), there is no such support to guide macropinocytic cups externally. These morphological and dynamical features that are distinct from other endocytic processes indicate a mechanism unique to macropinocytosis that remains to be elucidated

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