Time dependence of cellular responses to dynamic and complex strain fields

Area of Science:

• Cellular Mechanobiology
• Biophysics
• Tissue Engineering

Background:

• Cellular responses to mechanical stimuli are crucial for tissue development and disease.
• Understanding how cells sense and adapt to complex, dynamic mechanical environments is essential.

Purpose of the Study:

• To investigate fibroblast mechanoresponse to cyclically changing strain directions.
• To elucidate cellular sensing mechanisms under spatially non-uniform strain fields.
• To determine the influence of strain history on cellular reorientation.

Main Methods:

• Developed a polydimethylsiloxane microfluidic stretcher array for complex cell stretching experiments.
• Applied a spatially non-uniform strain field with cyclically switched stretching directions (11-hour intervals over 55 hours).
• Utilized advanced imaging and staining for detailed cellular analysis.

Main Results:

• Fibroblasts successfully reoriented to perpendicular strain directions repeatedly.
• Cellular reorientation perpendicular to strain decreased over successive cycles.
• Alignment perpendicular to strain gradients increased, indicating distinct time scales for strain and strain gradient responses.
• No major irreversible cellular changes were observed, preserving sensing and reorientation capabilities.

Conclusions:

• Cellular mechanoresponse exhibits time-dependent adaptation to dynamic and complex mechanical cues.
• The history of strain field dynamics influences cellular realignment behavior.
• Distinct time scales govern cellular responses to strain versus strain gradients, with gradient sensing being slower.