Surface tension-induced mechanotransduction in keratinocytes influences fibroblast activity and dermal matrix composition.

OBJECTIVE: Human skin is a highly dynamic organ capable of sensing and responding to mechanical stimuli through tightly regulated communication between the epidermis and dermis. Daily mechanical forces-such as stretching and compression-modulate skin structure and function via mechanotransduction pathways. Central to this process are the mechanosensitive Piezo channels, which convert mechanical tension into electrochemical signals. While the role of Piezo channels in epidermal keratinocytes has been established, it remains unclear whether mechanical tension at the skin's surface can influence deeper dermal responses. METHODS: In this study, we examined whether Piezo-mediated mechanotransduction in keratinocytes affects fibroblast activity and extracellular matrix (ECM) remodelling in the dermis. We applied controlled mechanical tension to the skin surface by the application of cosmetic products on the stratum corneum and measured key features of fibroblast activity and dermal matrix composition. RESULTS: We showed that generating surface tension-induced mechanotransduction in keratinocytes is consistent with the activation of Piezo channels and molecular changes in markers from distinct compartments, including the epidermal protein E-cadherin and dermal ECM proteins such as fibronectin and collagen III. These alterations suggest activation of downstream signalling pathways that may influence dermal fibroblasts, leading to remodelling of key ECM proteins including fibronectin and collagen III, while elastin levels remained unchanged. CONCLUSION: Our findings support the hypothesis that mechanical cues at the epidermal level, sensed via Piezo channels, may participate in interlayer communication and be associated with ECM remodelling in the dermis, supporting the hypothesis of a potential epidermis-to-dermis mechanotransduction axis in human skin.