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Mechanosensing of substrate thickness.

Yu-Chun Lin¹, Dhananjay T Tambe, Chan Young Park

¹Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics

|January 15, 2011

Summary

Cellular function is influenced by substrate thickness, not just stiffness. The cell's lateral size determines how it senses substrate thickness, impacting its behavior and forces.

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Area of Science:

Cell biology
Biophysics
Materials science

Background:

Cellular structure and function are critically dependent on the microenvironment, particularly substrate stiffness.
Substrate thickness is often assumed to be negligible, treated as semi-infinite, but this assumption is increasingly challenged.

Purpose of the Study:

To investigate the role of substrate thickness in cell mechanosensing.
To identify the characteristic length scale governing the influence of substrate thickness on cell behavior.
To understand how cells perceive and respond to variations in substrate thickness.

Main Methods:

Investigated cell responses (spreading area, stiffness, contractile forces) on substrates of varying thicknesses.
Analyzed the relationship between substrate thickness, lateral cell size, and apparent substrate stiffness.
Compared mechanosensing of substrate thickness over the cell's lateral dimension versus localized point forces.

Main Results:

The lateral cell size acts as the characteristic length scale for substrate thickness mechanosensing.
Apparent substrate stiffness increases significantly as thickness approaches lateral cell dimensions, exceeding intrinsic stiffness.
Cells exhibit altered spreading area, stiffness, and contractile forces in response to changes in apparent stiffness due to substrate thickness.

Conclusions:

Substrate thickness significantly influences cell behavior when its dimension is comparable to the cell's lateral size.
Mechanosensing of substrate thickness is primarily mediated by traction forces distributed across the cell's lateral dimension.
The findings challenge the semi-infinite substrate assumption and highlight the importance of considering substrate thickness in cell-environment interactions.