Work

Molecular dynamics model of mechanophore sensors for biological force measurement

Year: 2024

Type: article

Abstract: Cellular forces regulate an untold spectrum of living processes, such as cell migration, gene expression, and ion conduction. However, a quantitative description of mechanical control remains elusive due to the lack of general, live-cell tools to measure discrete forces between biomolecules. Here we introduce a computational pipeline for force measurement that leverages well-defined, tunable release of a mechanically activated small molecule fluorophore. These sensors are characterized using a multiscale approach combining equilibrium and steered QM/MM molecular dynamics models to capture the chemical, mechanical, and conformational transitions underlying force activation thresholds on a nano Newton scale. We find that chemical modification of the mechanophore and variation of its biomolecular tethers can tune the rate-determining step for fluorophore release and adjust the mechanochemical activation barrier. The models offer a new molecular framework for calibrated, programmable biomolecular force reporting within the live-cell regime, opening new opportunities to study mechanical phenomena in biological systems.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e41178

Authors: Sumit Mittal, Rongsheng E. Wang, Robert Ros, Alison E. Ondrus, Abhishek Singharoy

Institutions: VIT Bhopal University, Temple University, Arizona State University, University of Illinois Chicago

Language: English

Topic: Cellular Mechanics and Interactions

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,100