Keratocytes migrate against flow with a roly-poly-like mechanism

Area of Science:

• Cell Biology
• Biophysics
• Fluid Dynamics

Background:

• Cell migration is influenced by various mechanical cues, including fluid flow.
• The mechanisms underlying cell orientation in flow, such as active versus passive processes, are not fully understood.
• Leukocyte migration against flow is often considered active, mediated by integrin mechanotransduction.

Purpose of the Study:

• To investigate the flow mechanotaxis of fish epithelial keratocytes.
• To determine whether cell orientation in flow is an active or passive process.
• To elucidate the role of cell morphology in flow-induced orientation.

Main Methods:

• Observation of fish keratocyte behavior under controlled shear stresses.
• Development of a mechanical model based on cell morphology (hemisphere with a wide thin sheet).
• Analysis of hydrodynamic torque generated by cell shape and flow interaction.

Main Results:

• Keratocytes exhibit upstream or downstream orientation at shear stresses of tens of dyn cm⁻².
• Cell morphology, specifically the bulbous trailing edge, generates hydrodynamic torque stabilizing upstream orientation.
• The leading edge destabilizes upstream orientation, leading to two distinct phenotypes.
• A simple mechanical model accurately predicts the observed orientation phenotypes without adjustable parameters.

Conclusions:

• Keratocyte flow mechanotaxis is a passive phenomenon driven by the mechanical interaction of fluid flow with cell morphology.
• The observed orientation is governed by hydrodynamic torques, analogous to a roly-poly toy's stability.
• This passive mechanism suggests that active physiological functions or evolutionary pressures may not be necessary for keratocyte orientation in flow.