Curvotaxis directs cell migration through cell-scale curvature landscapes

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cells dynamically adapt to environmental cues for survival and function.
• Cellular microenvironments often feature complex topographical variations, including curvature.
• Existing cellular sensing mechanisms primarily focus on chemical or stiffness gradients.

Purpose of the Study:

• To identify and characterize a novel cellular response to substrate curvature.
• To elucidate the underlying molecular and mechanical mechanisms of this response.
• To establish cell-scale curvature as a significant physical cue in cellular behavior.

Main Methods:

• Fabrication of ultra-smooth sinusoidal surfaces with controlled curvature modulations.
• Live cell imaging to monitor cell migration and behavior on engineered topographies.
• Functional assays including cytoskeletal disruption and nuclear manipulation.
• Analysis of focal adhesions, nuclear shape, and gene expression in response to curvature.

Main Results:

• Adherent cells demonstrate directed migration, avoiding convex regions and favoring concave valleys.
• Curvotaxis is mediated by a nucleus-cytoskeleton interplay, with the nucleus acting as a mechanical sensor.
• Substrate curvature influences focal adhesion dynamics, nuclear morphology, and gene expression patterns.
• Cellular response to curvature is observed across different cell types (data not shown).

Conclusions:

• Curvotaxis represents a newly discovered cellular mechanism for navigating topographical landscapes.
• The cell nucleus plays a critical role in sensing and responding to substrate curvature.
• Cell-scale curvature is identified as a fundamental physical cue influencing cell behavior and potentially tissue development.