Tether extrusion from red blood cells: integral proteins unbinding from cytoskeleton

Area of Science:

• Biophysics
• Cell Biology
• Mechanobiology

Background:

• Red blood cells (RBCs) possess a unique membrane-cytoskeleton structure crucial for their function.
• Understanding the mechanical properties of this linkage is vital for cell integrity and disease research.

Purpose of the Study:

• To investigate the mechanical strength of RBC membrane-cytoskeleton adhesion and detachment dynamics.
• To elucidate the role of ATP in membrane tether extrusion and retraction.

Main Methods:

• Utilizing hydrodynamical flows to extract membrane tethers from RBCs attached to a microneedle.
• Monitoring tether extrusion and retraction dynamics under varying flow velocities (forces) across multiple cycles.
• Comparing tether dynamics in healthy, ATP-depleted, and ATP-inhibited RBCs.

Main Results:

• Healthy RBCs exhibit slow, reproducible tether extrusion and retraction.
• ATP-depleted/inhibited RBCs show an aging phenomenon, with impaired retraction and increased resistance to tether growth.
• Tether extrusion velocity (L) follows a nonlinear relationship with extrusion force (f), explained by a model of membrane-cytoskeleton association dynamics.
• The permeation regime, rather than sliding, governs extrusion dynamics, increasing membrane tension and tether narrowing.

Conclusions:

• Adenosine triphosphate (ATP) is critical for the proper retraction of extruded membrane tethers onto the RBC body.
• ATP depletion perturbs membrane-cytoskeleton linkage dynamics, leading to cellular aging and impaired mechanical responses.
• The study provides insights into the forces governing RBC membrane mechanics and the importance of cellular energy for maintaining structural integrity.