Bidirectional mechanobiology between cells and their local extracellular matrix probed by atomic force microscopy

Area of Science:

• Cellular and Tissue Mechanics
• Biophysics
• Biomaterials Science

Background:

• Mechanical interactions between cells and the extracellular matrix (ECM) are crucial for tissue development, homeostasis, repair, and disease.
• Atomic Force Microscopy (AFM) enables quantitative mechanical probing at the nanoscale, advancing cell and tissue mechanics research.

Purpose of the Study:

• To review how AFM has advanced the understanding of cell and ECM mechanobiology, focusing on soft tissues.
• To highlight AFM's role in elucidating cell-ECM bidirectional interactions and their implications in health and disease.

Main Methods:

• Utilizing Atomic Force Microscopy (AFM) to quantitatively measure mechanical properties and forces at the nanometer/micrometer scale.
• Analyzing AFM data from various biological samples, including soft acinar tissues (mammary, pulmonary).
• Investigating cell-ECM interactions, intrinsic cell micromechanics, and ECM properties post-decellularization.

Main Results:

• AFM revealed cell-type-specific intrinsic micromechanics and the role of β1 integrin/FAK(Y397) signaling and actomyosin cytoskeleton in cell mechanoresponses.
• ECM micromechanics vary by anatomical compartment, potentially influencing tissue function and cell differentiation.
• AFM identified key mechanoregulatory proteins (MMP14, α3β1 integrin) and clarified the role of altered mechanics in pathologies.

Conclusions:

• AFM is instrumental in understanding the mechanobiology of cells, ECM, and their interactions, particularly in soft tissues.
• Cellular and ECM mechanics are critical determinants of tissue function, differentiation, and disease progression.
• AFM provides valuable insights into the molecular mechanisms underlying tissue development and pathology.