Mechanical checkpoint for persistent cell polarization in adhesion-naive fibroblasts

Area of Science:

• Cell Biology
• Biophysics
• Developmental Biology

Background:

• Cell polarization is vital for multicellular development.
• The roles of substrate mechanics and biochemistry in cell polarity are not fully understood.

Purpose of the Study:

• To define the minimal requirements for triggering and sustaining cell polarization.
• To quantify the mechanical forces involved in cell polarization.

Main Methods:

• Utilized a novel single-cell approach with nonadhered round fibroblast cells.
• Investigated stiffness sensing via localized integrin-mediated cues.
• Developed a physical model for cell polarization.

Main Results:

• Single localized integrin-mediated cues are necessary and sufficient for shape polarization.
• A minimal traction force of 56 ± 1.6 pN is required for persistent polarization.
• Polarization kinetics increase with substrate stiffness, involving actomyosin redistribution and centrosome reorientation.

Conclusions:

• Defined minimal adhesive requirements and mechanical checkpoints for cell shape and organelle polarization.
• Demonstrated that local inhibition of actin/myosin activity can trigger and sustain polarization.
• Highlighted the critical role of these polarization mechanisms in tissue and cell development.