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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Cellular Responses to Nanoscale Topography Mediated Through the RhoA/ROCK Pathway.
Erik N Schaumann1, Nam Heon Cho1, Teri W Odom1,2
1Department of Chemistry, Northwestern University, Evanston, IL, 60208, United States.
Small (Weinheim an Der Bergstrasse, Germany)
|August 18, 2025
Summary
The RhoA/ROCK pathway regulates cell responses to nanotopography by controlling cellular tension. Modulating this pathway affects cell shape, actin organization, and endocytosis when interacting with nanoscale features.
Area of Science:
- Biomaterials Science
- Cell Biology
- Biophysics
Background:
- Nanotopography significantly influences cellular behaviors, including cytoskeletal organization and endocytosis.
- Cellular responses to topographical cues can lead to systemic effects like inflammation and implant rejection.
- The specific biological pathways mediating these nanotopographical responses are not well understood.
Purpose of the Study:
- To investigate the role of the RhoA/ROCK pathway in regulating cellular responses to nanotopographical features.
- To determine how modulating RhoA activity impacts cellular tension and subsequent interactions with nanoscale patterns.
- To establish a link between cell mechanics regulators and responses to nanotopography.
Main Methods:
- Utilized 2D arrays of hemispherical gold nanoparticles in conjunction with epithelial cells.
- Manipulated RhoA activity (up- and down-regulation) to observe its effects on cellular responses.
- Analyzed cellular tension, membrane conformality, actin reorganization, endocytosis, and focal adhesion formation.
Main Results:
- Elevated RhoA activity correlated with increased cellular tension, reduced membrane conformality, and decreased actin reorganization and endocytosis.
- Increased cellular tension induced large focal adhesions, which are atypical for substrate patterns.
- Reduced RhoA activity led to greater membrane conformality around nanoparticles and enhanced colocalization of actin and endocytosis with nanoparticle sites.
Conclusions:
- The RhoA/ROCK pathway is a key regulator of cellular responses to nanotopographical cues.
- Cellular tension, modulated by RhoA, dictates how cells interact with and adapt to nanoscale surface features.
- This study provides a crucial link between molecular regulators of cell mechanics and cellular mechanotransduction in response to nanotopography.
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