Accelerated epithelial layer healing induced by tactile anisotropy in surface topography

Area of Science:

• Cell biology
• Biophysics
• Tissue engineering

Background:

• Mammalian cells sense substrate topography for directional guidance.
• Extracellular matrix (ECM) topography is often disordered, affecting cell response.
• The impact of topographic order gradients in noisy environments on cell behavior is not well understood.

Purpose of the Study:

• To investigate how cells respond to topographical signals in a noisy environment.
• To identify and characterize a novel cell guidance mechanism based on topographic order gradients.
• To explore the role of topographic order in regulating cell proliferation and wound healing.

Main Methods:

• Fabrication of rationally designed substrates with controlled topographic order gradients.
• Live-cell imaging and analysis of isolated cells and cell ensembles (fibroblasts, epithelial cells).
• Mathematical modeling to simulate cell behavior and wound healing processes.

Main Results:

• Discovery of 'morphotaxis': cells move along gradients of topographic order distortion.
• Demonstration that morphotaxis occurs in response to varying gradient strengths and directions.
• Observation that topographic order influences cell cycle progression, affecting proliferation.
• Mature epithelia integrate topographic order variations over large distances.
• Mathematical model confirms morphotaxis and noise-dependent proliferation enhance wound healing.

Conclusions:

• Morphotaxis is a novel cell guidance mechanism responding to topographic order gradients.
• Topographic order influences both cell migration and proliferation, impacting tissue repair.
• The interplay between morphotaxis and noise-driven proliferation offers a strategy for improved wound healing.