Mechanosensing

To maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues...

Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into biochemical signaling cascades within cells, subsequently leading to various cellular responses in a stimulus-dependent manner. At the surface of extracellular environment and cell cytoplasm exist several ion channel families that are activated by mechanical signals to direct intracellular events. One of such channel is formed by transient receptor potential cation channel subfamily V member, TRPV4 that is known to act as a mechanosensor in wide variaty of tissues and control ion-influx in a spatio-temporal way...

Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments, beneath the previously identified α-actinin cross-linked actin filaments, appear critical for adhesion maturation and controlled cell motility, whereas the adjacent Tpm3...

Osteocytes, the most abundant cell type in bone, play a crucial role in mechanosensation and signaling for bone formation and resorption. These cells reside within a complex lacuno-canalicular network (OLCN). Osteocyte signaling is reduced under diabetic conditions, and both type 1 and type 2 diabetes lead to reduced bone turnover, perturbed bone composition, and increased fracture risk. We hypothesized that this reduced bone turnover, and altered bone composition with diabetes is associated with reduced OLCN architecture and connectivity...

No abstract text is available yet for this article.

Skeletal muscles and bones are closely connected anatomically and functionally. Age-related degeneration in these tissues is associated with physical disability in the elderly and significantly impacts their quality of life. Understanding the mechanisms of age-related musculoskeletal tissue degeneration is crucial for identifying molecular targets for therapeutic interventions for skeletal muscle atrophy and osteoporosis. The Hippo pathway is a recently identified signaling pathway that plays critical roles in development, tissue homeostasis, and regeneration...

No abstract text is available yet for this article.

Mechanosensation of plasma membrane tension by various mechanoresponsive machineries is crucial for regulating stem cell fate, cell adhesion, and tissue morphogenesis. Here, we present a protocol for evaluating plasma membrane stretching during the differentiation of Drosophila ovarian cyst using a fluorescent lipid tension reporter (Flipper-TR). We describe the steps for microphone setup, ovary dissection, Flipper-TR staining, fluorescence lifetime imaging microscopy imaging, and image processing and analysis...

Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration...

Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cells from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis...

This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered...

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hind paw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur...

The reversible unfolding and refolding of proteins is a regulatory mechanism of tissue elasticity and signalling used by cells to sense and adapt to extracellular and intracellular mechanical forces. However, most of these proteins exhibit low mechanical stability, posing technical challenges to the characterization of their conformational dynamics under force. Here, we detail step-by-step instructions for conducting single-protein nanomechanical experiments using ultra-stable magnetic tweezers, which enable the measurement of the equilibrium conformational dynamics of single proteins under physiologically relevant low forces applied over biologically relevant timescales...

Sensory signaling pathways use adaptation to dynamically respond to changes in their environment. Here, we report the mechanism of sensory adaptation in the Pil-Chp mechanosensory system, which the important human pathogen Pseudomonas aeruginosa uses to sense mechanical stimuli during surface exploration. Using biochemistry, genetics, and cell biology, we discovered that the enzymes responsible for adaptation, a methyltransferase and a methylesterase, are segregated to opposing cell poles as P. aeruginosa explore surfaces...

A complete map of the external sense organs shows how fruit fly larvae detect different aspects of their environment.

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes...

Induced Tregs (iTregs) have great promise in adoptive immunotherapy for treatment of autoimmune diseases. This report investigates the impacts of substrate stiffness on human Treg induction, providing a powerful yet simple approach to improving production of these cells. Conventional CD4+ human T cells were activated on materials of different elastic modulus and cultured under suppressive conditions. Enhanced Treg induction was observed on softer materials as early as 3 days following activation and persisted for multiple weeks...

Synthetic signaling receptors enable programmable cellular responses coupling with customized inputs. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling de novo-designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors...

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2 . Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch...

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes...