dictyNews

Electronic Edition

Volume 48, number 23

November 4, 2022



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Abstracts

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Particle-based model of mechanosensory contractility kit assembly



Plaza-Rodriguez A., Nguyen LTS, Robinson DN, Iglesias, PA. 





Biophys. J., in press

DOI:https://doi.org/10.1016/j.bpj.2022.10.031



Cell shape-change processes, such as proliferation, polarization, 

migration, and cancer metastasis, rely on a dynamic network of 

macromolecules. The proper function of this network enables 

mechanosensation, the ability of cells to sense and respond to 

mechanical cues. Myosin II and cortexillin I, critical elements of the 

cellular mechanosensory machinery, preassemble in the cytoplasm 

of Dictyostelium cells into complexes that we have termed contractility 

kits (CKs). Two IQGAP proteins then differentially regulate the 

mechanoresponsiveness of the cortexillin I-myosin II elements within 

CKs. To investigate the mechanism of CK self-assembly and gain 

insight into possible molecular means for IQGAP regulation, we 

developed a coarse-grained excluded-volume molecular model in 

which all protein polymers are represented by nm-sized spheres 

connected by spring-like links. The model is parameterized using 

experimentally measured parameters acquired through Fluorescence 

Cross-Correlation Spectroscopy (FCCS) and Fluorescence Correlation 

Spectroscopy (FCS), which describe the interaction affinities and 

diffusion coefficients for individual molecular components, and which 

have also been validated via several orthogonal methods. Simulations 

of wild-type and null-mutant conditions implied that the temporal order 

of assembly of these kits is dominated by myosin II dimer formation 

and that IQGAP proteins mediate cluster growth. Additionally, our 

simulations predicted the existence of “ambiguous” CKs that incorporate 

both classes of IQGAPs, and we confirmed this experimentally using 

FCCS. The model serves to describe the formation of the CKs and 

how their assembly enables and regulates mechanosensation at the 

molecular level.





Submitted by Doug Robinson [[log in to unmask]]

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[End dictyNews, volume 48, number 23]