Aging-associated decline in vascular smooth muscle cell mechanosensation is mediated by Piezo1 channel.

Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs' ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum, and transcriptome analyses.

Single-Cell Analysis of Contractile Forces in iPSC-Derived Cardiomyocytes: Paving the Way for Precision Medicine in Cardiovascular Disease.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in cardiac disease modeling, drug screening, and regenerative medicine. Furthermore, patient-specific iPSC-CMS can be tested for personalized medicine. To provide a deeper understanding of the contractile force dynamics of iPSC-CMs, we employed Atomic Force Microscopy (AFM) as an advanced detection tool to distinguish the characteristics of force dynamics at a single cell level.

Aging-associated Decline in Vascular Smooth Muscle Cell Mechanosensation is Mediated by Piezo1 Channel.

Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs' ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum and transcriptome analyses.

Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1.

Mechanical overload of the vascular wall is a pathological hallmark of life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at the unicellular level of vascular smooth muscle cells (VSMC) is undefined. Here we show defective mechano-phenotype signatures of VSMC in AAA measured with ultrasound tweezers-based micromechanical system and single-cell RNA sequencing technique.

Surface presentation of the noncanonical Wnt5a motif to cytotoxic CD8 T-cells promotes their mechanotransduction and activation.

We report here strategic functionalization of the Wnt5a mimetic peptide ligand Foxy5 on a polydimethylsiloxane elastomer substrate to enhance the mechanotransduction and activation of cytotoxic CD8 T cells by triggering the noncanonical Wnt signaling. This new mechanoregulatory ligand platform can be widely applied in the fundamental research of mechano-immunology and further the development of novel immunotherapies.

The cellular mechanobiology of aging: from biology to mechanics.

Aging is a chronic, complicated process that leads to degenerative physical and biological changes in living organisms. Aging is associated with permanent, gradual physiological cellular decay that affects all aspects of cellular mechanobiological features, including cellular cytoskeleton structures, mechanosensitive signaling pathways, and forces in the cell, as well as the cell's ability to sense and adapt to extracellular biomechanical signals in the tissue environment through mechanotransduction. These mechanobiological changes in cells are directly or indirectly responsible for dysfunctions and diseases in various organ systems, including the cardiovascular, musculoskeletal, skin, and immune systems.

Mechanical Forces Regulate Asymmetric Vascular Cell Alignment.

Mechanical forces between cells and their microenvironment critically regulate the asymmetric morphogenesis and physiological functions in vascular systems. Here, we investigated the asymmetric cell alignment and cellular forces simultaneously in micropatterned endothelial cell ring-shaped sheets and studied how the traction and intercellular forces are involved in the asymmetric vascular morphogenesis. Tuning the traction and intercellular forces using different topographic geometries of symmetric and asymmetric ring-shaped patterns regulated the vascular asymmetric morphogenesis in vitro.

The Interplay Between Cell-Cell and Cell-Matrix Forces Regulates Cell Migration Dynamics.

Cells in vivo encounter and exert forces as they interact with the extracellular matrix (ECM) and neighboring cells during migration. These mechanical forces play crucial roles in regulating cell migratory behaviors. Although a variety of studies have focused on describing single-cell or the collective cell migration behaviors, a fully mechanistic understanding of how the cell-cell (intercellular) and cell-ECM (extracellular) traction forces individually and cooperatively regulate single-cell migration and coordinate multicellular movement in a cellular monolayer is still lacking.

Cellogram: On-the-Fly Traction Force Microscopy.

Traction force microscopy (TFM) derives maps of cell-generated forces, typically in the nanonewton range, transmitted to the extracellular environment upon actuation of complex biological processes. In traditional approaches, force rendering requires a terminal, time-consuming step of cell deadhesion to obtain a reference image. A conceptually opposite approach is provided by reference-free methods, opening to the on-the-fly generation of force maps from an ongoing experiment.

Energy-Mediated Machinery Drives Cellular Mechanical Allostasis.

Allostasis is a fundamental biological process through which living organisms achieve stability via physiological or behavioral changes to protect against internal and external stresses, and ultimately better adapt to the local environment. However, an full understanding of cellular-level allostasis is far from developed. By employing an integrated micromechanical tool capable of applying controlled mechanical stress on an individual cell and simultaneously reporting dynamic information of subcellular mechanics, individual cell allostasis is observed to occur through a biphasic process; cellular mechanics tends to restore to a stable state through a mechanoadaptative process with excitative biophysical activity followed by a decaying adaptive phase.

Nanotopographic Regulation of Human Mesenchymal Stem Cell Osteogenesis.

Mesenchymal stem cell (MSC) differentiation can be manipulated by nanotopographic interface providing a unique strategy to engineering stem cell therapy and circumventing complex cellular reprogramming. However, our understanding of the nanotopographic-mechanosensitive properties of MSCs and the underlying biophysical linkage of the nanotopography-engineered stem cell to directed commitment remains elusive. Here, we show that osteogenic differentiation of human MSCs (hMSCs) can be largely promoted using our nanoengineered topographic glass substrates in the absence of dexamethasone, a key exogenous factor for osteogenesis induction.