The aim of this study was to investigate the healing characteristics and the underlying signalling pathway of human dermal fibroblasts under the influence of pulsed electrical stimulation (PES). Primary human dermal fibroblasts were seeded on polypyrrole-coated polyester fabrics and subjected to four different PES protocols. The parameters of the rectangular pulse included potential intensity (50 and 100 mV/mm) and stimulation time (pulse width 300 s within a period of 600 s, and pulse width 10 s within a period of 1200 s). Our study revealed that PES moderately improved the ability of the cells to migrate in association with a statistically significant (p < 0.05) increase of FGF2 secretion by the PES-exposed fibroblasts. These exposed fibroblasts were able to contract collagen gel matrix up to 48 h and this collagen gel contraction paralleled an increase in α-SMA mRNA expression and protein production from the PES-exposed fibroblasts. Interestingly, the effect of PES on the human fibroblasts involved the Smad signalling pathway, as we observed higher levels of phosphorylated Smad2 and Smad3 in the stimulated groups compared to the control groups. Overall, this study demonstrated that PES modulates fibroblast activities through the Smad signalling pathway, thus providing new mechanistic insights related to the use of PES to promote wound healing in humans. Copyright © 2015 John Wiley & Sons, Ltd.

Mechanical stimulation plays a crucial role in numerous biological activities, including tissue development, regeneration and remodeling. Understanding how cells respond to their mechanical microenvironment is vital for investigating mechanotransduction with adequate spatial and temporal resolution. Cell force sensing—also known as mechanosensation or mechanotransduction—involves force transmission through the cytoskeleton and mechanochemical signaling. Insights into cell–extracellular matrix interactions and mechanotransduction are particularly relevant for guiding biomaterial design in tissue engineering. To establish a foundation for mechanical biomedicine, this review will provide a comprehensive overview of cell mechanotransduction mechanisms, including the structural components essential for effective mechanical responses, such as cytoskeletal elements, force-sensitive ion channels, membrane receptors and key signaling pathways. It will also discuss the clutch model in force transmission, the role of mechanotransduction in both physiology and pathological contexts, and biomechanics and biomaterial design. Additionally, we outline analytical approaches for characterizing forces at cellular and subcellular levels, discussing the advantages and limitations of each method to aid researchers in selecting appropriate techniques. Finally, we summarize recent advancements in cell force sensing and identify key challenges for future research. Overall, this review should contribute to biomedical engineering by supporting the design of biomaterials that integrate precise mechanical information.

Integrins coupled with other proteins form protein complexes named focal adhesions (FA) which are considered as the primary sites for cellular forces transduction during cell stable adhesion. Cell traction forces transmitted by FAs and integrin tensions inside FAs have been extensively studied. However, it remains unknown whether integrins outside FAs can transmit tension, and if so, what is the tension range. We previously developed a tension sensor named tension gauge tether (TGT). To calibrate integrin tensions outside FAs, here we applied multiplex TGT (mTGT) to simultaneously monitor integrin tensions at separate levels. mTGT unambiguously revealed that integrins outside FAs also transmit tension after FA formation. These tensions are mainly located in the range of 43 ~ 54 pN which is lower than integrin tensions inside FAs. Integrin tensions both inside and outside FAs substantially contribute to bulk cellular forces and they respond independently to actin and myosin II inhibition, serum deprivation and microtubule inhibition, indicating their different tension sources and independent dynamics. Our work identified integrin tensions outside FAs and calibrated the tension range for the first time. We also demonstrated that mTGT is a valuable tool to monitor integrin tension profile in a broad detection range of 10 ~ 60 pN.