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Maurizio Pesce, Elisa Messina, Isotta Chimenti, Antonio Paolo Beltrami
The life-long story of the heart starts concomitantly with primary differentiation events occurring in multipotent progenitors located in the so called heart tube. This initially tubular structure starts a looping process which leads to formation of the final four chambered heart with a primary contribution of geometric and position-associated cell sensing. While this establishes the correct patterning of the final cardiac structure, it also feedbacks to fundamental cellular machineries controlling proliferation and differentiation, thus ensuring a coordinated restriction of cell growth and a myocyte terminal differentiation...
October 13, 2016: Stem Cells and Development
Andrew W Holle, Alistair J McIntyre, Jared Kehe, Piyumi Wijesekara, Jennifer L Young, Ludovic G Vincent, Adam J Engler
Human mesenchymal stem cells (hMSCs) receive differentiation cues from a number of stimuli, including extracellular matrix (ECM) stiffness. The pathways used to sense stiffness and other physical cues are just now being understood and include proteins within focal adhesions. To rapidly advance the pace of discovery for novel mechanosensitive proteins, we employed a combination of in silico and high throughput in vitro methods to analyze 47 different focal adhesion proteins for cryptic kinase binding sites. High content imaging of hMSCs treated with small interfering RNAs for the top 6 candidate proteins showed novel effects on both osteogenic and myogenic differentiation; Vinculin and SORBS1 were necessary for stiffness-mediated myogenic and osteogenic differentiation, respectively...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Julia C Quindlen, Henryk K Stolarski, Matthew D Johnson, Victor H Barocas
The Pacinian corpuscle (PC) is a dermal mechanoreceptor that responds to high-frequency (20-1000 Hz) vibrations. The PC's structure allows transmission of vibrations through its layers (lamellae) to the centrally-located nerve fiber (neurite). This work combines mechanical models of the PC with an electrochemical model of peripheral nerves to simulate the tactile response of the entire system. A three-stage model of response to a vibratory input was developed, consisting of (1) outer core mechanics, (2) inner core mechanics, and (3) neurite electrochemistry...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Arianna Mauretti, Noortje A M Bax, Mieke H van Marion, Marie José Goumans, Cecilia Sahlgren, Carlijn V C Bouten
For emerging cardiac regeneration strategies, it is essential to know if and how cardiac stem cells sense and respond to the mechanical stimuli provided by their environment in the beating heart. Here, we study the response to cyclic strain of undifferentiated and predifferentiated human cardiomyocyte progenitor cells (CMPCs), as well as the formation and activation of the cellular structures involved in mechanosensing, that we termed 'mechanosome'. Once verified that the applied uniaxial cyclic strain (10%, 0...
September 12, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Lorenzo Marcucci, Carlo Reggiani
Almost 60 years ago Andrew Huxley with his seminal paper (Huxley, 1957) laid the foundation of modern muscle modeling, linking chemical to mechanical events. He described mechanics and energetics of muscle contraction through the cyclical attachment and detachment of myosin motors to the actin filament with ad-hoc assumptions on the dependence of the rate constants on the strain of the myosin motors. That relatively simple hypothesis is still present in recent models, even though with several modifications to adapt the model to the different experimental constraints which became subsequently available...
2016: Frontiers in Physiology
Marjolein B M Meddens, Elvis Pandzic, Johan A Slotman, Dominique Guillet, Ben Joosten, Svenja Mennens, Laurent M Paardekooper, Adriaan B Houtsmuller, Koen van den Dries, Paul W Wiseman, Alessandra Cambi
Podosomes are cytoskeletal structures crucial for cell protrusion and matrix remodelling in osteoclasts, activated endothelial cells, macrophages and dendritic cells. In these cells, hundreds of podosomes are spatially organized in diversely shaped clusters. Although we and others established individual podosomes as micron-sized mechanosensing protrusive units, the exact scope and spatiotemporal organization of podosome clustering remain elusive. By integrating a newly developed extension of Spatiotemporal Image Correlation Spectroscopy with novel image analysis, we demonstrate that F-actin, vinculin and talin exhibit directional and correlated flow patterns throughout podosome clusters...
October 10, 2016: Nature Communications
Alberto Garcia, Jose F Rodriguez Matas, Manuela T Raimondi
Recent evidence suggests that mechanical deformation of the cell nucleus regulates the nuclear import of the transcriptional activators of genes involved in primary physiological cell responses such as stem cell differentiation. In addition, this nuclear mechanosensing response is de-regulated in pathological states, such as cancer and neurodegeneration. One hypothesis that could greatly advance the field is that the deformation of the nuclear envelope activates nuclear pore complexes through a direct mechanical link...
October 10, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Kishore K Bokka, Edwin C Jesudason, David Warburton, Sharon R Lubkin
Peristalsis begins in the lung as soon as the smooth muscle (SM) forms, and persists until birth. As the prenatal lung is filled with liquid, SM action can, through lumen pressure, deform tissues far from the immediately adjacent tissues. Stretching of embryonic tissues has been shown to have potent morphogenetic effects. We hypothesize that these effects are at work in lung morphogenesis. In order to refine that broad hypothesis in a quantitative framework, we geometrically analyse cell shapes in an epithelial tissue, and individual cell deformations resulting from peristaltic waves that completely occlude the airway...
October 6, 2016: Interface Focus
Dibyendu Kumar Das, Robert J Mallis, Jonathan S Duke-Cohan, Rebecca E Hussey, Paul W Tetteh, Mark Hilton, Gerhard Wagner, Matthew J Lang, Ellis Reinherz
The pre-T cell receptor (preTCR) is a pTα-β heterodimer functioning in early αβ T-cell development. Although once thought to be ligand-autonomous, recent studies show that preTCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe preTCR bonding with pMHC at the single molecule level. Like the αβTCR, the preTCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes, and exploiting allosteric control regulated via the Cβ FG loop region...
October 5, 2016: Journal of Biological Chemistry
Guang-Kui Xu, Bo Li, Xi-Qiao Feng, Huajian Gao
Deciphering the mechanisms underlying the high sensitivity of cells to mechanical microenvironments is crucial for understanding many physiological and pathological processes, e.g., stem cell differentiation and cancer cell metastasis. Here, a cytoskeletal tensegrity model is proposed to study the reorientation of polarized cells on a substrate under biaxial cyclic deformation. The model consists of four bars, representing the longitudinal stress fibers and lateral actin network, and eight strings, denoting the microfilaments...
October 4, 2016: Biophysical Journal
Georgia Dalagiorgou, Christina Piperi, Christos Adamopoulos, Urania Georgopoulou, Antonios N Gargalionis, Anastasia Spyropoulou, Ilianna Zoi, Marjan Nokhbehsaim, Anna Damanaki, James Deschner, Efthimia K Basdra, Athanasios G Papavassiliou
Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation...
October 3, 2016: Cellular and Molecular Life Sciences: CMLS
Simon J Attwood, Ernesto Cortes, Alexander William M Haining, Benjamin Robinson, Danyang Li, Julien Gautrot, Armando Del Río Hernández
Cells are known to respond to physical cues from their microenvironment such as matrix rigidity. Discrete adhesive ligands within flexible strands of fibronectin connect cell surface integrins to the broader extracellular matrix and are thought to mediate mechanosensing through the cytoskeleton-integrin-ECM linkage. We set out to determine if adhesive ligand tether length is another physical cue that cells can sense. Substrates were covalently modified with adhesive arginylglycylaspartic acid (RGD) ligands coupled with short (9...
September 30, 2016: Scientific Reports
Maryam Riaz, Marie Versaevel, Danahe Mohammed, Karine Glinel, Sylvain Gabriele
Despite the importance of matrix rigidity on cell functions, many aspects of the mechanosensing process in highly migratory cells remain elusive. Here, we studied the migration of highly motile keratocytes on culture substrates with similar biochemical properties and rigidities spanning the range between soft tissues (~kPa) and stiff culture substrates (~GPa). We show that morphology, polarization and persistence of motile keratocytes are regulated by the matrix stiffness over seven orders of magnitude, without changing the cell spreading area...
September 28, 2016: Scientific Reports
Wei Deng, Yan Xu, Wenchun Chen, David S Paul, Anum K Syed, Matthew A Dragovich, Xin Liang, Philip Zakas, Michael C Berndt, Jorge Di Paola, Jerry Ware, Francois Lanza, Christopher B Doering, Wolfgang Bergmeier, X Frank Zhang, Renhao Li
Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIbα subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane 'Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance...
September 27, 2016: Nature Communications
E Xiao, Chider Chen, Yi Zhang
Mesenchymal stem cells (MSCs) are multipotent adult stem cells. MSCs and their potential for use in regenerative medicine have been investigated extensively. Recently, the mechanisms by which MSCs detect mechanical stimuli have been described in detail. As in other cell types, both mechanosensitive channels, such as transient receptor potential melastatin 7 (TRPM7), and the cytoskeleton, including actin and actomyosin, have been implicated in mechanosensation in MSCs. This review will focus on discussing the precise role of TRPM7 and the cytoskeleton in mechanosensation in MSCs...
2016: Stem Cell Research & Therapy
Karan M Shah, Matt M Stern, Amber R Stern, Janak L Pathak, Nathalie Bravenboer, Astrid D Bakker
The aim of this paper is to present several popular methods for in vitro culture of osteocytes and osteocyte cell lines. Osteocytes are located extremely suitably within the calcified bone matrix to sense mechanical signals, and are equipped with a multitude of molecular features that allow mechanosensing. However, osteocytes are more than specialized mechanosensing cells. Several signaling molecules are preferentially produced by osteocytes, and osteocytes hold a tight reign over osteoblast and osteoclast formation and activity, but also have a role as endocrine cell, communicating with muscles or organs as remote as the kidneys...
2016: BoneKEy Reports
Renata Buda, Yunxiao Liu, Jin Yang, Smitha Hegde, Keiran Stevenson, Fan Bai, Teuta Pilizota
For most cells, a sudden decrease in external osmolarity results in fast water influx that can burst the cell. To survive, cells rely on the passive response of mechanosensitive channels, which open under increased membrane tension and allow the release of cytoplasmic solutes and water. Although the gating and the molecular structure of mechanosensitive channels found in Escherichia coli have been extensively studied, the overall dynamics of the whole cellular response remain poorly understood. Here, we characterize E...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
David E Koser, Amelia J Thompson, Sarah K Foster, Asha Dwivedy, Eva K Pillai, Graham K Sheridan, Hanno Svoboda, Matheus Viana, Luciano da F Costa, Jochen Guck, Christine E Holt, Kristian Franze
During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain...
September 19, 2016: Nature Neuroscience
Stacey Lee, Sanjay Kumar
Mechanotransduction is the process through which cells survey the mechanical properties of their environment, convert these mechanical inputs into biochemical signals, and modulate their phenotype in response. These mechanical inputs, which may be encoded in the form of extracellular matrix stiffness, dimensionality, and adhesion, all strongly influence cell morphology, migration, and fate decisions. One mechanism through which cells on planar or pseudo-planar matrices exert tensile forces and interrogate microenvironmental mechanics is through stress fibers, which are bundles composed of actin filaments and, in most cases, non-muscle myosin II filaments...
2016: F1000Research
Kenneth K Y Ho, Lap Man Lee, Allen P Liu
All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner...
2016: Scientific Reports
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