Abstract

Cyclic stretch applied to cells induces the reorganization of stress fibers. However, the correlation between the reorganization of stress fiber subtypes and strain-dependent responses of the cytoplasm and nucleus has remained unclear. Here, we investigated the dynamic involvement of stress fiber subtypes in the orientation and elongation of cyclically stretched epithelial cells. We applied uniaxial cyclic stretches at 5%, 10%, and 15% strains to cells followed by the release of the mechanical stretch. Dorsal, transverse arcs, and peripheral stress fibers were mainly involved in the cytoplasm responses whereas perinuclear cap fibers were associated with the reorientation and elongation of the nucleus. Dorsal stress fibers and transverse arcs rapidly responded within 15 min regardless of the strain magnitude to facilitate the subsequent changes in the orientation and elongation of the cytoplasm. The cyclic stretches induced the additional formation of perinuclear cap fibers and their increased number was almost maintained with a slight decline after 2-h-long stretch release. The slow formation and high stability of perinuclear cap fibers were linked to the slow reorientation kinetics and partial morphology recovery of nucleus in the presence or absence of cyclic stretches. The reorganization of stress fiber subtypes occurred in accordance with the reversible distribution of myosin II. These findings allowed us to propose a model for stretch-induced responses of the cytoplasm and nucleus in epithelial cells based on different mechanoadaptive properties of stress fiber subtypes.

Highlights

  • Cyclic stretch applied to cells induces the reorganization of stress fibers

  • The duration of our cyclic stretches was limited to 2 h since 10% of stretched cells at 15% strain for 2 h were found to be apoptotic after 24 h (Supplementary Fig. S4A,B)

  • To understand how SF subtypes are involved in strain-dependent reorientation of the cytoplasm and nucleus to uniaxial cyclic stretches, we examined the reorganization of SF subtypes through the fluorescence staining of SF-associated molecules

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Summary

Introduction

Cyclic stretch applied to cells induces the reorganization of stress fibers. the correlation between the reorganization of stress fiber subtypes and strain-dependent responses of the cytoplasm and nucleus has remained unclear. The reorganization of stress fiber subtypes occurred in accordance with the reversible distribution of myosin II These findings allowed us to propose a model for stretch-induced responses of the cytoplasm and nucleus in epithelial cells based on different mechanoadaptive properties of stress fiber subtypes. SFs that are distributed at different cellular locations with different structures can be divided into four subtypes: perinuclear cap fiber, dorsal stress fiber, transverse arc, and ventral stress fiber. Dorsal stress fibers are devoid of myosin II in the uniform polarity of their structure suggesting the non-contractile properties They are polymerized at one end that is attached to FAC, whereas the other end is connected to transverse arcs (curved-shape SF subtypes) which exhibit the Scientific Reports | (2020) 10:18684. These studies have clarified the crucial role of the SF reorganization in maintaining cellular mechanohomeostasis in cell-stretching conditions

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