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The Mechanics of Poro-Elastic Contractile Actomyosin Networks As a Model System of the Cell Cytoskeleton
Published on: March 10, 2023
843
Particle-based model of mechanosensory contractility kit assembly
Alma I Plaza-Rodríguez1, Ly T S Nguyen2, Douglas N Robinson2
1Department of Biophysics, Johns Hopkins University, Baltimore, Maryland.
Biophysical Journal
|October 23, 2022
Summary
Cellular contractility kits (CKs), essential for mechanosensation, self-assemble via myosin II dimer formation. IQGAP proteins regulate CK growth and mechanoresponsiveness, enabling cells to sense and respond to mechanical cues.
Area of Science:
- Cell biology
- Biophysics
- Molecular dynamics
Background:
- Cellular processes like migration and metastasis depend on macromolecular networks.
- Mechanosensation, the ability to respond to mechanical cues, is crucial for cell function.
- Myosin II and cortexillin I form preassembled complexes called contractility kits (CKs) in Dictyostelium cells.
Purpose of the Study:
- To investigate the self-assembly mechanism of CKs.
- To understand how IQGAP proteins regulate CK mechanoresponsiveness.
- To model the molecular basis of CK formation and mechanosensation.
Main Methods:
- Developed a coarse-grained excluded volume molecular model representing protein polymers as spheres.
- Parameterized the model using experimental data from fluorescence cross-correlation spectroscopy (FCS) and fluorescence correlation spectroscopy (FCS).
- Validated model parameters using orthogonal experimental methods.
Main Results:
- Simulations indicated myosin II dimer formation dominates CK temporal assembly order.
- IQGAP proteins were shown to mediate CK cluster growth.
- Predicted and experimentally confirmed the existence of "ambiguous" CKs containing both IQGAP types.
Conclusions:
- The developed model accurately describes CK formation and regulation.
- CK assembly is crucial for enabling and regulating cellular mechanosensation at the molecular level.
- IQGAP proteins play a key role in modulating CK behavior and cellular mechanosensing.
