A structural bio-chemo-mechanical model for vascular smooth muscle cell traction force microscopy.

Area of Science:

• Biomedical Engineering
• Cellular Mechanics
• Computational Biology

Background:

• Altered vascular smooth muscle cell (VSMC) contractility contributes to arterial dysfunction.
• Traction force microscopy (TFM) is key for quantifying VSMC contraction but faces challenges in translating single-cell data to tissue-scale behavior due to complex mechanisms.

Purpose of the Study:

• To develop a computational model that integrates biochemical and biomechanical factors in TFM.
• To create a framework for interpreting TFM data and linking cellular mechanisms to tissue-level function.

Main Methods:

• A computational model was developed incorporating biochemical signaling, actomyosin fiber contraction, cytoskeletal networks, and substrate displacement.
• The model integrates four key interacting components of the cell traction process.
• The model was validated against experimental data for VSMCs under various perturbations.

Main Results:

• The model successfully recapitulated experimental data for VSMCs.
• It provides a flexible framework for describing TFM and linking biochemical and biomechanical phenomena at the single-cell level.
• The model demonstrates the ability to interpret TFM data mechanistically.

Conclusions:

• The developed bio-chemo-mechanical model offers a novel tool for interpreting TFM data.
• It facilitates hypothesis evaluation, data interpolation, and the translation of single-cell findings to multi-scale tissue models.
• This framework enhances the mechanistic understanding of VSMC contractility and arterial function.