Epithelial cells experience long lasting loads of different magnitudes and rates. How they adapt to these loads strongly impacts tissue health. Yet, much remains unknown about their stress evolution under sustained strain. Here, by subjecting cell pairs to sustained strain, we report a bimodal stress response, where in addition to the typically observed stress relaxation, a subset of cells exhibits a dynamic tensioning process with significant elevation in stress within 100s, resembling active pulling-back in muscle fibers. Strikingly, the fraction of cells exhibiting tensioning increases with increasing strain rate. The tensioning response is accompanied by actin remodeling, and perturbation to actin abrogates it, supporting cell contractility’s role in the response. Collectively, our data show that epithelial cells adjust their tensional states over short timescales in a strain-rate dependent manner to adapt to sustained strains, demonstrating that the active pulling-back behavior could be a common protective mechanism against environmental stress.
more »
« less
Characterization of the strain-rate–dependent mechanical response of single cell–cell junctions
Cell–cell junctions are essential components in multicellular structures and often experience strains of different magnitudes and rates. However, their mechanical behavior is currently underexplored due to the lack of techniques to quantitatively characterize junctional stress–strain relationships. We developed a polymeric microstructure to strain the mutual junction of a single cell pair while simultaneously recording the junction stress and observed previously unseen strain-rate–dependent junction responses. We showed that cytoskeleton growth could relax the stress buildup and prevent junction failure at low strain rates, while high strain rates led to synchronized junction failures at remarkably large strains (over 200%). We expect this platform and our biophysical understanding to form the foundation for the rate-dependent mechanics of cell–cell junctions.
more » « less- PAR ID:
- 10212503
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 118
- Issue:
- 7
- ISSN:
- 0027-8424
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
Abstract It is becoming increasingly clear that mechanical stress in adhesive junctions plays a significant role in dictating the fate of cell–cell attachment under physiological conditions. Targeted disruption of cell–cell junctions leads to multiple pathological conditions, among them the life‐threatening autoimmune blistering disease pemphigus vulgaris (PV). The dissociation of cell–cell junctions by autoantibodies is the hallmark of PV, however, the detailed mechanisms that result in tissue destruction remain unclear. Thus far, research and therapy in PV have focused primarily on immune mechanisms upstream of autoantibody binding, while the biophysical aspects of the cell–cell dissociation process leading to acantholysis are less well studied. In work aimed at illuminating the cellular consequences of autoantibody attachment, it is reported that externally applied mechanical stress mitigates antibody‐induced monolayer fragmentation and inhibits p38 MAPK phosphorylation activated by anti‐Dsg3 antibody. Further, it is demonstrated that mechanical stress applied externally to cell monolayers enhances cell contractility via RhoA activation and promotes the strengthening of cortical actin, which ultimately mitigates antibody‐induced cell–cell dissociation. The study elevates understanding of the mechanism of acantholysis in PV and shifts the paradigm of PV disease development from a focus solely on immune pathways to highlight the key role of physical transformations at the target cell.
-
more » « less
Abstract Mapping strain fields in visually opaque structural composites—for which failure is often sudden, irreparable, and even catastrophic—requires techniques to locate and record regions of stress, fatigue, and incipient failure. Many composite materials are transparent in the terahertz spectral region, but their strain history is often too subtle to recover. Here, terahertz metamaterials with strain‐severable junctions are introduced that can identify structurally compromised regions of composite materials. Specifically, multilayer arrays of aluminum meta‐atoms are designed and fabricated as strip dipole antennas with a terahertz frequency resonance and a strong response to cross‐polarized radiation that disappears when local stress irreversibly breaks their bowtie‐shaped junction. By spatially mapping the local polarimetric response of this metamaterial as a function of global strain, the regions of local stress extrema experienced by a visually opaque material may be visualized. This proof‐of‐concept demonstration heralds the opportunity for embedding metamaterial laminates within composites to record and recover their strain‐dependent history of fatigue.
-
Strain rate of stretch affects crossbridge detachment during relaxation of intact cardiac trabeculaeJohnson, Daniel M (Ed.)more » « less
Mechanical Control of Relaxation refers to the dependence of myocardial relaxation on the strain rate just prior to relaxation, but the mechanisms of enhanced relaxation are not well characterized. This study aimed to characterize how crossbridge kinetics varied with strain rate and time-to-stretch as the myocardium relaxed in early diastole. Ramp-stretches of varying rates (amplitude = 1% muscle length) were applied to intact rat cardiac trabeculae following a load-clamp at 50% of the maximal developed twitch force, which provides a first-order estimate of ejection and coupling to an afterload. The resultant stress-response was calculated as the difference between the time-dependent stress profile between load-clamped twitches with and without a ramp-stretch. The stress-response exhibited features of the step-stretch response of activated, permeabilized myocardium, such as distortion-dependent peak stress, rapid force decay related to crossbridge detachment, and stress recovery related to crossbridge recruitment. The peak stress was strain rate dependent, but the minimum stress and the time-to-minimum stress values were not. The initial rapid change in the stress-response indicates enhanced crossbridge detachment at higher strain rates during relaxation in intact cardiac trabeculae. Physiologic considerations, such as time-varying calcium, are discussed as potential limitations to fitting these data with traditional distortion-recruitment models of crossbridge activity.
-
Adhesive tapes are versatile and widely used yet lack adhesion strength due to their tendency to fail via peeling, a weak failure mode. A tape with surprising adhesive properties is the recluse spider's 50 nm-thin silk ribbon with a 1 : 150 aspect ratio. Junctions of these microscopic sticky tapes can withstand the material's tensile failure stress of ≈1 GPa. We modeled these natural tape–tape junctions and revealed a bi-modal failure behavior, critically dependent on the two tapes’ intersection angle. One mode leads to regular, low-strength peeling failure, while the other causes the junction to self-strengthen, eliminating the inherent weakness in peeling. This self-strengthening mechanism locks the two tapes together, increasing the junction strength by 550% and allowing some junctions to remain intact after tensile failure. This impressive adhesive strength of tapes has never before been observed or predicted. We found that recluse spiders make tape junctions with pre-stress to force the locked, high-strength failure mode. We used this approach to make junctions with synthetic adhesive tapes that overcame the weak peeling failure.more » « less
