High-pressure environments exert significant impact on cellular survival. In Saccharomyces cerevisiae, two endoplasmic reticulum (ER)-localized proteins, Ehg1 and Ehg2, are essential for growth under 25 MPa hydrostatic pressure. Ehg1 is a cytoplasmic peripheral membrane protein containing a critical PXFP motif for its function. Ehg2 is a two-pass transmembrane protein characterized by conserved luminal domains, essential N-glycosylation sites, and a vital cytoplasmic GVPS motif. Both proteins stabilize nutrient permeases by preventing their degradation under high-pressure conditions, thereby maintaining nutrient uptake. These findings reveal a unique adaptive strategy in which ER-localized proteins preserve membrane protein integrity during mechanical stress.

This paper describes the development of an artificial mechanosensitive ion channel that mimics the function of natural membrane proteins. The designed molecules feature a one-dimensional architecture consisting of alternating hydrophilic and hydrophobic segments. Upon incorporation into a bilayer membrane, the hydrophobic segments self-assemble to form a functional ion channel. Due to the relatively weak interactions between the hydrophobic segments, the assembly state is sensitive to changes in membrane tension caused by osmotic pressure, resulting in modulation of ion permeability. Through rational molecular design, both responsiveness to the membrane tension and ion selectivity have been successfully achieved. The structural design and functional behaviors of these artificial mechanosensitive ion channels are overviewed.

Aortic wall thickening under hypertension is regarded as a smooth muscle adaptation to restore homeostasis. However, the cellular mechanisms initiating and terminating this response remain unclear. Hypertension induces mechanical stimuli—such as hydrostatic pressure, interstitial shear stress, and cyclic stretch—that may trigger cellular adaptation. We hypothesized that cyclic stretch transmitted via stress fibers regulates both the onset and cessation of this process. To test this, we quantified strain along stress fiber orientation under hypertensive and adaptive conditions. Our results suggest that stress fibers modulate nuclear mechanics and act as mechanosensors in vascular remodeling during hypertension.

Homeostasis in living organisms is regulated by mechanical factors, including pressure. However, the mechanisms by which pressure influences cellular functions remain unclear, partly due to methodological limitations. Here, we describe a system capable of applying controlled hydrostatic pressure to cultured cells and of evaluating their responses. Under high-pressure conditions, we observed alterations in cell morphology, subcellular protein localization, and gene expression profiles. These findings provide new insights into pressure-induced cellular regulation and demonstrate the utility of our system as a platform for elucidating mechanobiological processes mediated by pressure stimuli.

The high-hydrostatic pressure device uses high pressure to destroy all cells in tissue while preserving its structure. The target disease is congenital giant pigmented nevus，a benign skin tumor. We have begun investigating a new treatment method that involves killing all cells contained in the excised nevus and then regenerating the dermis through reimplantation. After confirming its efficacy in preclinical trials and conducting a first-in-human clinical trial，we initiated a physician-initiated clinical trial aimed at obtaining medical device approval. This trial confirmed that skin regeneration is possible using pressurized nevi and cultured epidermis. Currently, we are conducting basic research to apply this device to inactivate malignant bone tumors and facilitate reimplantation.

This article introduces the concept of “deep-sea-inspired chemistry,” which derives chemical innovation from the extreme physicochemical and biological conditions found in the deep sea. Three representative examples are discussed: (1) baroplastics that undergo pressure-induced order–disorder transitions, (2) bottom-up nanoemulsification mimicking hydrothermal vent dynamics, and (3) cellulases evolved in deep-sea microbes. These systems demonstrate how pressure, thermal gradients, and enzymatic function in deep-sea environments can inspire sustainable materials and processes. This approach proposes a paradigm shift in ocean utilization—from a resource economy to a knowledge-driven circular economy—highlighting the deep sea as a new frontier for chemical technology.

松本 凌