Macropinocytosis is clathrin-independent endocytosis and allows internalization of large volume of extracellular fluid. Dictyostelium discoideum and tumor cells show constitutive macropinocytosis for uptake of nutrients from extracellular fluid. With help of recent advance of microscopy for 4D observation, macropinocytosis has been considered to be driven by self-organizing pattern of actin polymerization on the membrane. However, it remains still unknown how crown-like (or macropinositosis cup) structure forms, how it closes and what chemical reactions make it possible.
From theoretical perspective, we introduce a mathematical model based on phase-field method for simulating 3D morphodynamics of macropinocytosis. The proposed model with the help of GPU enables reaction-diffusion process of membrane localized proteins and large membrane deformation simultaneously.
Simulation results indicate that simple chemical reactions including actin polymerization lead to drastic membrane deformation, which results in an engulfment of extracellular fluid. In addition, depending on parameters, not only macropinocytosis but also CDR (circular dorsal raffle) like behaviors appear.
This study provides a new insight for constitutive macropinocytosis as a self-organization phenomenon via feedback between drastic deformation of membrane and reaction-diffusion on it.