Mechanisms controlling cell size and shape during isotropic cell spreading.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Cell motility is crucial for development and physiology.
• It involves complex interactions between cell membrane physical forces and actin cytoskeleton biochemistry.
• Understanding these interactions is key to deciphering cell behavior.

Purpose of the Study:

• To develop a computational model analyzing the interplay of physical and biochemical factors in cell motility.
• To simulate the isotropic spreading phase of mammalian fibroblasts.
• To investigate how membrane forces and actin dynamics regulate cell shape and size.

Main Methods:

• A three-dimensional stochastic multiscale model was constructed.
• The model incorporates actin filament remodeling reactions influenced by membrane forces (surface resistance, bending energy).
• Numerical simulations and experimental validation using Cytochalasin D and Latrunculin A were performed.

Main Results:

• The model accurately captures experimentally observed isotropic cell spreading.
• It predicts that increased capping protein concentration reduces cell spread radius.
• Actin monomer concentration affects the rate of spreading, validating model predictions.

Conclusions:

• Membrane physical forces primarily control cell shape during spreading.
• Actin cytoskeleton dynamics govern the rate of cell spreading (cell size).
• A balance between biochemical and biophysical properties determines cell size and shape, providing mechanistic insights into cell motility regulation.