Single-pericyte nanomechanics measured by contraction cytometry

Area of Science:

• Biophysics
• Cell Biology
• Biomedical Engineering

Background:

• Pericytes regulate microvascular blood flow by constricting/dilating vessels.
• The mechanisms by which pericytes sense and respond to their microenvironment are largely unknown.
• Aberrant pericyte contraction is linked to various diseases and injury susceptibility.

Purpose of the Study:

• To develop a high-throughput method for quantifying single-cell pericyte contraction forces.
• To investigate the role of the mechanical microenvironment in pericyte survival during hypoxia.
• To identify potential therapeutic targets for mitigating blood flow reduction after hypoxic injury.

Main Methods:

• Development of a hydrogel-based pericyte contraction cytometer.
• Quantification of contraction forces from murine and human pericytes in diverse microenvironments.
• Assessment of pericyte responses to vasoconstricting/vasodilating stimuli and hypoxic conditions.

Main Results:

• The pericyte contraction cytometer successfully measured single-cell forces.
• Murine pericyte survival in hypoxia depends on the mechanical microenvironment.
• Extracellular cofilin-1 released pericytes from hypoxia-induced contractile rigor, preventing blood flow reduction.

Conclusions:

• The pericyte contraction cytometer is a valuable tool for studying pericyte biophysics and drug screening.
• Mechanical cues significantly influence pericyte behavior and survival under hypoxic stress.
• Cofilin-1 presents a novel therapeutic strategy for restoring blood flow post-hypoxic injury.