Dec 02, 2014

Volume 107Issue 11p2479-2744, E01-E02, L33-L36
Open Archive
Cover picture: Integrin β1 colocalizes with EGF-bound EGF receptor (EGFR) signaling complexes, preferentially with those at the cell periphery. NIH-3T3 cells stably expressing EGFRs were incubated on surfaces micropatterned with EGF (red channel). EGFRs cluster in patterned regions where EGF is presented, as revealed by stimulated receptor tyrosine kinase activity in those regions (blue channel). Integrins also accumulate in regions of clustered EGFRs, although preferentially at the peripheral locations (green channel). Experimental details: surface-adhering cells were fixed, permeabilized, and immunolabeled with an anti-phosphotyrosine 4G10 antibody and an A633-tagged secondary antibody and also immunolabeled with an anti-β1 integrin primary antibody and an A488-tagged secondary antibody. For more information, see the article by Singhai et al. on page 2639....
Cover picture: Integrin β1 colocalizes with EGF-bound EGF receptor (EGFR) signaling complexes, preferentially with those at the cell periphery. NIH-3T3 cells stably expressing EGFRs were incubated on surfaces micropatterned with EGF (red channel). EGFRs cluster in patterned regions where EGF is presented, as revealed by stimulated receptor tyrosine kinase activity in those regions (blue channel). Integrins also accumulate in regions of clustered EGFRs, although preferentially at the peripheral locations (green channel). Experimental details: surface-adhering cells were fixed, permeabilized, and immunolabeled with an anti-phosphotyrosine 4G10 antibody and an A633-tagged secondary antibody and also immunolabeled with an anti-β1 integrin primary antibody and an A488-tagged secondary antibody. For more information, see the article by Singhai et al. on page 2639.


  • Editorial

    Biophysical Journal Special Issue: Focus on Quantitative Cell Biology

    • David W. Piston
    Biophysics has thrived by applying reductionist approaches to unravel biological mechanisms, and to this day, such approaches continue to bring fresh insights into the functions of cells and organisms. X-ray crystallography, molecular dynamics simulations, single molecule microscopy, and single channel recordings are but a few of the powerful and varied biophysical techniques widely used in today’s biomedical research labs to elucidate the structure and functions of biomolecules. Of course, we also know that biomolecules do not function on their own, but work instead through complex interactive networks within cells.

Biophysical Letter

  • Biophysical Letter

    Association Rates of Membrane-Coupled Cell Adhesion Molecules

    • Timo Bihr,
    • Susanne Fenz,
    • Erich Sackmann,
    • Rudolf Merkel,
    • Udo Seifert,
    • Kheya Sengupta,
    • Ana-Sunčana Smith
    Thus far, understanding how the confined cellular environment affects the lifetime of bonds, as well as the extraction of complexation rates, has been a major challenge in studies of cell adhesion. Based on a theoretical description of the growth curves of adhesion domains, we present a new (to our knowledge) method to measure the association rate kon of ligand-receptor pairs incorporated into lipid membranes. As a proof of principle, we apply this method to several systems. We find that the kon for the interaction of biotin with neutravidin is larger than that for integrin binding to RGD or sialyl Lewisx to E-selectin.

New and Notable

  • New and Notable

    Gathering Support for Critical Mass: Interleukin 4 Receptor Signaling Requires Clustering in Endosomes

    • Stefan N. Constantinescu
    The signaling paradigm for cytokine receptors consists of ligand binding to the extracellular domains of cell-surface-exposed receptors. This first even leads to either dimerization or conformational change of a preformed inactive dimer (1,2), which in turn leads to reciprocal activation of Janus kinase proteins (JAK) that are appended to the cytosolic juxtamembrane regions of receptors. Once JAKs become activated they phosphorylate tyrosines on cytosolic domains of receptors and on JAKs themselves.
  • New and Notable

    New and Notable: Uncertainty Quantification

    • James B. Bassingthwaighte
    Johnston et al. (1), in this issue of the Biophysical Journal, show us that simple calculations are not so simple when there is uncertainty in the underlying input data. They illustrate this using an on-line CALADIS calculator where the uncertainty in a variable or parameter is represented using a probability density function (pdf). CALADIS calculations are done using Monte Carlo, drawing 20,000 (or other) successive samples from the pdfs for the components of the equations, and using them to add, subtract, multiply, or divide.
  • New and Notable

    Switching from Protease-Independent to Protease-Dependent Cancer Cell Invasion

    • Lijuan He,
    • Denis Wirtz
    Metastasis of tumor cells, starting from their infiltration of local tissues, is responsible for the vast majority of cancer-related deaths (1). Understanding the molecular mechanisms of cancer cell invasion and migration during metastasis is critical for the development of novel therapies for cancer treatment. Cells have been proposed to employ either protease-dependent or protease-independent modes for migration and invasion (2). In response to matrix properties, moving cells degrade the extracellular matrix (ECM) molecules by upregulating or activating specific enzymes, such as matrix metalloproteinases (MMPs), in cell protrusions confronting the dense mesh of the ECM (e.g., lamellipodia for cells on 2D substrates (3), dendritic protrusions of cells in a 3D matrix (4), and invadopodia for cells crossing the basement membrane (5)).
  • New and Notable

    Pinning Down the EGF Receptor

    • Thomas M. Jovin
    According to leading investigators in the field of cellular signal transduction, the epidermal growth factor (EGF) receptor (EGFR, ErbB1, HER1), ubiquitously encountered in signaling mechanisms and thus in human tumors, is the best studied yet least prototypic of receptor tyrosine kinases in general (1). This perception arises primarily from the fact that activation of the EGFR is thought to be conformational/allosteric, i.e., not requiring covalent modifications at or near the active site (2). However, a number of outstanding, perplexing questions exist that might still place the EGFR in the well known but poorly understood category.
  • New and Notable

    Cellular Diffraction: Scanning X-Ray Nanodiffraction from Living Cells

    • Joseph Strzalka
    Cellular diffraction, or scanning x-ray nanodiffraction applied to cells, is a new technique that promises insight into cellular organization at length scales of 1–200 nm, covering the features of molecules and organelles. Filling a niche between the length scales probed by optical and electron microscopy, cellular diffraction rasters a nanofocused x-ray beam across living cells in an aqueous medium and records a two-dimensional image of, for instance, the small-angle scattering signal at each position.
  • New and Notable

    Systems Perspective on Mechanobiology: Producing the Right Proteins in the Right Place at the Right Time

    • Ulrich S. Schwarz
    Mechanical forces are ubiquitous in biological systems and the field of mechanobiology has emerged with research subjects being investigated from the molecular through the cellular to the tissue level. However, there is a well-defined experimental observation on the cell biological level that can be considered as the defining core of this field, namely the finding that the morphology of adherent cells is strongly determined by the mechanical stiffness of their extracellular environment and that the cells sense this stiffness by self-generated forces (1).

Biophysical Reviews

  • Biophysical Review

    Using Fluctuation Analysis to Establish Causal Relations between Cellular Events without Experimental Perturbation

    • Erik S. Welf,
    • Gaudenz Danuser
    Experimental perturbations are commonly used to establish causal relationships between the molecular components of a pathway and their cellular functions; however, this approach suffers inherent limitations. Especially in pathways with a significant level of nonlinearity and redundancy among components, such perturbations induce compensatory responses that obscure the actual function of the targeted component in the unperturbed pathway. A complementary approach uses constitutive fluctuations in component activities to identify the hierarchy of information flow through pathways.
  • Biophysical Review

    The Value of Mechanistic Biophysical Information for Systems-Level Understanding of Complex Biological Processes Such as Cytokinesis

    • Thomas D. Pollard
    This review illustrates the value of quantitative information including concentrations, kinetic constants and equilibrium constants in modeling and simulating complex biological processes. Although much has been learned about some biological systems without these parameter values, they greatly strengthen mechanistic accounts of dynamical systems. The analysis of muscle contraction is a classic example of the value of combining an inventory of the molecules, atomic structures of the molecules, kinetic constants for the reactions, reconstitutions with purified proteins and theoretical modeling to account for the contraction of whole muscles.
  • Biophysical Review

    Early Events in Cell Spreading as a Model for Quantitative Analysis of Biomechanical Events

    • Haguy Wolfenson,
    • Thomas Iskratsch,
    • Michael P. Sheetz
    In this review, we focus on the early events in the process of fibroblast spreading on fibronectin matrices of different rigidities. We present a focused position piece that illustrates the many different tests that a cell makes of its environment before it establishes mature matrix adhesions. When a fibroblast is placed on fibronectin-coated glass surfaces at 37°C, it typically spreads and polarizes within 20-40 min primarily through αvβ3 integrin binding to fibronectin. In that short period, the cell goes through three major phases that involve binding, integrin activation, spreading, and mechanical testing of the surface.

Cell Biophysics

  • Article

    Dynamics and Interaction of Interleukin-4 Receptor Subunits in Living Cells

    • Hetvi Gandhi,
    • Remigiusz Worch,
    • Kristina Kurgonaite,
    • Martin Hintersteiner,
    • Petra Schwille,
    • Christian Bökel,
    • Thomas Weidemann
    It has long been established that dimerization of Interleukin-4 receptor (IL-4R) subunits is a pivotal step for JAK/STAT signal transduction. However, ligand-induced complex formation at the surface of living cells has been challenging to observe. Here we report an experimental assay employing trisNTA dyes for orthogonal, external labeling of eGFP-tagged receptor constructs that allows the quantification of receptor heterodimerization by dual-color fluorescence cross-correlation spectroscopy. Fluorescence cross-correlation spectroscopy analysis at the plasma membrane shows that IL-4R subunit dimerization is indeed a strictly ligand-induced process.
  • Article

    3D Traction Stresses Activate Protease-Dependent Invasion of Cancer Cells

    • Aereas Aung,
    • Young N. Seo,
    • Shaoying Lu,
    • Yingxiao Wang,
    • Colin Jamora,
    • Juan C. del Álamo,
    • Shyni Varghese
    Cell invasion and migration that occurs, for example, in cancer metastasis is rooted in the ability of cells to navigate through varying levels of physical constraint exerted by the extracellular matrix. Cancer cells can invade matrices in either a protease-independent or a protease-dependent manner. An emerging critical component that influences the mode of cell invasion is the traction stresses generated by the cells in response to the physicostructural properties of the extracellular matrix. In this study, we have developed a reference-free quantitative assay for measuring three-dimensional (3D) traction stresses generated by cells during the initial stages of invasion into matrices exerting varying levels of mechanical resistance.
  • Article

    The Interplay between Cell Wall Mechanical Properties and the Cell Cycle in Staphylococcus aureus

    • Richard G. Bailey,
    • Robert D. Turner,
    • Nic Mullin,
    • Nigel Clarke,
    • Simon J. Foster,
    • Jamie K. Hobbs
    The nanoscale mechanical properties of live Staphylococcus aureus cells during different phases of growth were studied by atomic force microscopy. Indentation to different depths provided access to both local cell wall mechanical properties and whole-cell properties, including a component related to cell turgor pressure. Local cell wall properties were found to change in a characteristic manner throughout the division cycle. Splitting of the cell into two daughter cells followed a local softening of the cell wall along the division circumference, with the cell wall on either side of the division circumference becoming stiffer.
  • Article

    3D Collagen Alignment Limits Protrusions to Enhance Breast Cancer Cell Persistence

    • Kristin M. Riching,
    • Benjamin L. Cox,
    • Max R. Salick,
    • Carolyn Pehlke,
    • Andrew S. Riching,
    • Susan M. Ponik,
    • Benjamin R. Bass,
    • Wendy C. Crone,
    • Yi Jiang,
    • Alissa M. Weaver,
    • Kevin W. Eliceiri,
    • Patricia J. Keely
    Patients with mammographically dense breast tissue have a greatly increased risk of developing breast cancer. Dense breast tissue contains more stromal collagen, which contributes to increased matrix stiffness and alters normal cellular responses. Stromal collagen within and surrounding mammary tumors is frequently aligned and reoriented perpendicular to the tumor boundary. We have shown that aligned collagen predicts poor outcome in breast cancer patients, and postulate this is because it facilitates invasion by providing tracks on which cells migrate out of the tumor.
  • Article

    Fiber-Dependent and -Independent Toxicity of Islet Amyloid Polypeptide

    • Diana E. Schlamadinger,
    • Andrew D. Miranker
    The 37-residue peptide hormone islet amyloid polypeptide (IAPP) plays a central role in diabetes pathology. Although its amyloid fiber aggregation kinetics and cytotoxicity to β-cells are well documented, few reports have directly assessed the role of fibers in cell-based toxicity experiments. Here, we report that amyloid formation of IAPP can be strongly inhibited by the extracellular environment of live cells. For example, fiber formation is more strongly suppressed in cell culture medium than in aqueous buffer.
  • Article

    A Refined Reaction-Diffusion Model of Tau-Microtubule Dynamics and Its Application in FDAP Analysis

    • Maxim Igaev,
    • Dennis Janning,
    • Frederik Sündermann,
    • Benedikt Niewidok,
    • Roland Brandt,
    • Wolfgang Junge
    Fluorescence decay after photoactivation (FDAP) and fluorescence recovery after photobleaching (FRAP) are well established approaches for studying the interaction of the microtubule (MT)-associated protein tau with MTs in neuronal cells. Previous interpretations of FDAP/FRAP data have revealed dwell times of tau on MTs in the range of several seconds. However, this is difficult to reconcile with a dwell time recently measured by single-molecule analysis in neuronal processes that was shorter by two orders of magnitude.
  • Article

    Diffusion within the Cytoplasm: A Mesoscale Model of Interacting Macromolecules

    • Fabio Trovato,
    • Valentina Tozzini
    Recent experiments carried out in the dense cytoplasm of living cells have highlighted the importance of proteome composition and nonspecific intermolecular interactions in regulating macromolecule diffusion and organization. Despite this, the dependence of diffusion-interaction on physicochemical properties such as the degree of poly-dispersity and the balance between steric repulsion and nonspecific attraction among macromolecules was not systematically addressed. In this work, we study the problem of diffusion-interaction in the bacterial cytoplasm, combining theory and experimental data to build a minimal coarse-grained representation of the cytoplasm, which also includes, for the first time to our knowledge, the nucleoid.
  • Article

    Long-Range Force Transmission in Fibrous Matrices Enabled by Tension-Driven Alignment of Fibers

    • Hailong Wang,
    • A.S. Abhilash,
    • Christopher S. Chen,
    • Rebecca G. Wells,
    • Vivek B. Shenoy
    Cells can sense and respond to mechanical signals over relatively long distances across fibrous extracellular matrices. Recently proposed models suggest that long-range force transmission can be attributed to the nonlinear elasticity or fibrous nature of collagen matrices, yet the mechanism whereby fibers align remains unknown. Moreover, cell shape and anisotropy of cellular contraction are not considered in existing models, although recent experiments have shown that they play crucial roles. Here, we explore all of the key factors that influence long-range force transmission in cell-populated collagen matrices: alignment of collagen fibers, responses to applied force, strain stiffening properties of the aligned fibers, aspect ratios of the cells, and the polarization of cellular contraction.
  • Article

    Role of Suspended Fiber Structural Stiffness and Curvature on Single-Cell Migration, Nucleus Shape, and Focal-Adhesion-Cluster Length

    • Sean Meehan,
    • Amrinder S. Nain
    It has been shown that cellular migration, persistence, and associated cytoskeletal arrangement are highly dependent on substrate stiffness (modulus: N/m2 and independent of geometry), but little is known on how cells respond to subtle changes in local geometry and structural stiffness (N/m). Here, using fibers of varying diameter (400, 700, and 1200 nm) and length (1 and 2 mm) deposited over hollow substrates, we demonstrate that single mouse C2C12 cells attached to single suspended fibers form spindle morphologies that are sensitive to fiber mechanical properties.
  • Computational Tools

    Explicit Tracking of Uncertainty Increases the Power of Quantitative Rule-of-Thumb Reasoning in Cell Biology

    • Iain G. Johnston,
    • Benjamin C. Rickett,
    • Nick S. Jones
    Back-of-the-envelope or rule-of-thumb calculations involving rough estimates of quantities play a central scientific role in developing intuition about the structure and behavior of physical systems, for example in so-called Fermi problems in the physical sciences. Such calculations can be used to powerfully and quantitatively reason about biological systems, particularly at the interface between physics and biology. However, substantial uncertainties are often associated with values in cell biology, and performing calculations without taking this uncertainty into account may limit the extent to which results can be interpreted for a given problem.
  • Article

    Dynamic Network Morphology and Tension Buildup in a 3D Model of Cytokinetic Ring Assembly

    • Tamara C. Bidone,
    • Haosu Tang,
    • Dimitrios Vavylonis
    During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes and bundled by cross-linking proteins. The myosin motors exert forces on the actin filaments, resulting in a net pulling of the nodes into a contractile ring, while cross-linking interactions help align actin filaments and nodes into a single bundle. We used these mechanisms in a three-dimensional computational model of contractile ring assembly, with semiflexible actin filaments growing from formins at cortical nodes, capturing of filaments by neighboring nodes, and cross-linking among filaments through attractive interactions.
  • Article

    Ligand-Mediated Friction Determines Morphodynamics of Spreading T Cells

    • Pierre Dillard,
    • Rajat Varma,
    • Kheya Sengupta,
    • Laurent Limozin
    Spreading of T cells on antigen presenting cells is a crucial initial step in immune response. Spreading occurs through rapid morphological changes concomitant with the reorganization of surface receptors and of the cytoskeleton. Ligand mobility and frictional coupling of receptors to the cytoskeleton were separately recognized as important factors but a systematic study to explore their biophysical role in spreading was hitherto missing. To explore the impact of ligand mobility, we prepared chemically identical substrates on which molecules of anti-CD3 (capable of binding and activating the T cell receptor complex), were either immobilized or able to diffuse.
  • Article

    Spatially Defined EGF Receptor Activation Reveals an F-Actin-Dependent Phospho-Erk Signaling Complex

    • Amit Singhai,
    • Devin L. Wakefield,
    • Kirsten L. Bryant,
    • Stephen R. Hammes,
    • David Holowka,
    • Barbara Baird
    We investigated the association of signaling proteins with epidermal growth factor (EGF) receptors (EGFR) using biotinylated EGF bound to streptavidin that is covalently coupled in an ordered array of micron-sized features on silicon surfaces. Using NIH-3T3 cells stably expressing EGFR, we observe concentration of fluorescently labeled receptors and stimulated tyrosine phosphorylation that are spatially confined to the regions of immobilized EGF and quantified by cross-correlation analysis. We observe recruitment of phosphorylated paxillin to activated EGFR at these patterned features, as well as β1-containing integrins that preferentially localize to more peripheral EGF features, as quantified by radial fluorescence analysis.
  • Article

    Self-Organizing Actomyosin Patterns on the Cell Cortex at Epithelial Cell-Cell Junctions

    • Thomas Moore,
    • Selwin K. Wu,
    • Magdalene Michael,
    • Alpha S. Yap,
    • Guillermo A. Gomez,
    • Zoltan Neufeld
    The behavior of actomyosin critically determines morphologically distinct patterns of contractility found at the interface between adherent cells. One such pattern is found at the apical region (zonula adherens) of cell-cell junctions in epithelia, where clusters of the adhesion molecule E-cadherin concentrate in a static pattern. Meanwhile, E-cadherin clusters throughout lateral cell-cell contacts display dynamic movements in the plane of the junctions. To gain insight into the principles that determine the nature and organization of these dynamic structures, we analyze this behavior by modeling the 2D actomyosin cell cortex as an active fluid medium.
  • Article

    Scanning X-Ray Nanodiffraction on Dictyostelium discoideum

    • Marius Priebe,
    • Marten Bernhardt,
    • Christoph Blum,
    • Marco Tarantola,
    • Eberhard Bodenschatz,
    • Tim Salditt
    We have performed scanning x-ray nanobeam diffraction experiments on single cells of the amoeba Dictyostelium discoideum. Cells have been investigated in 1), freeze-dried, 2), frozen-hydrated (vitrified), and 3), initially alive states. The spatially resolved small-angle x-ray scattering signal shows characteristic streaklike patterns in reciprocal space, which we attribute to fiber bundles of the actomyosin network. From the intensity distributions, an anisotropy parameter can be derived that indicates pronounced local variations within the cell.
  • Article

    How Long Should a System Be Observed to Obtain Reliable Concentration Estimates from the Measurement of Fluctuations?

    • Emiliano Pérez Ipiña,
    • Silvina Ponce Dawson
    The interior of cells is a highly fluctuating environment. Fluctuations set limits to the accuracy with which endogenous processes can occur. The physical principles that rule these limits also affect the experimental quantification of biophysical parameters in situ. The characterization of fluctuations, on the other hand, provides a way to quantify biophysical parameters. But as with any random process, enough data has to be collected to achieve a reliable quantitative description. In this article we study the accuracy with which intracellular concentrations can be estimated using fluorescence correlation spectroscopy.
  • Article

    Cytoplasmic Dynamics Reveals Two Modes of Nucleoid-Dependent Mobility

    • Stella Stylianidou,
    • Nathan J. Kuwada,
    • Paul A. Wiggins
    It has been proposed that forces resulting from the physical exclusion of macromolecules from the bacterial nucleoid play a central role in organizing the bacterial cell, yet this proposal has not been quantitatively tested. To investigate this hypothesis, we mapped the generic motion of large protein complexes in the bacterial cytoplasm through quantitative analysis of thousands of complete cell-cycle trajectories of fluorescently tagged ectopic MS2-mRNA complexes. We find the motion of these complexes in the cytoplasm is strongly dependent on their spatial position along the long axis of the cell, and that their dynamics are consistent with a quantitative model that requires only nucleoid exclusion and membrane confinement.
  • Article

    Mechanics of Individual Keratin Bundles in Living Cells

    • Jens-Friedrich Nolting,
    • Wiebke Möbius,
    • Sarah Köster
    Along with microtubules and microfilaments, intermediate filaments are a major component of the eukaryotic cytoskeleton and play a key role in cell mechanics. In cells, keratin intermediate filaments form networks of bundles that are sparser in structure and have lower connectivity than, for example, actin networks. Because of this, bending and buckling play an important role in these networks. Buckling events, which occur due to compressive intracellular forces and cross-talk between the keratin network and other cytoskeletal components, are measured here in situ.

Molecular Machines, Motors, and Nanoscale Biophysics

  • Article

    Dual Biochemical Oscillators May Control Cellular Reversals in Myxococcus xanthus

    • Erik Eckhert,
    • Padmini Rangamani,
    • Annie E. Davis,
    • George Oster,
    • James E. Berleman
    Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals.

Systems Biophysics

  • Article

    Amplitude Metrics for Cellular Circadian Bioluminescence Reporters

    • Peter C. St. John,
    • Stephanie R. Taylor,
    • John H. Abel,
    • Francis J. Doyle III
    Bioluminescence rhythms from cellular reporters have become the most common method used to quantify oscillations in circadian gene expression. These experimental systems can reveal phase and amplitude change resulting from circadian disturbances, and can be used in conjunction with mathematical models to lend further insight into the mechanistic basis of clock amplitude regulation. However, bioluminescence experiments track the mean output from thousands of noisy, uncoupled oscillators, obscuring the direct effect of a given stimulus on the genetic regulatory network.
  • Article

    Intrinsic Islet Heterogeneity and Gap Junction Coupling Determine Spatiotemporal Ca2+ Wave Dynamics

    • Richard K.P. Benninger,
    • Troy Hutchens,
    • W. Steven Head,
    • Michael J. McCaughey,
    • Min Zhang,
    • Sylvain J. Le Marchand,
    • Leslie S. Satin,
    • David W. Piston
    Insulin is released from the islets of Langerhans in discrete pulses that are linked to synchronized oscillations of intracellular free calcium ([Ca2+]i). Associated with each synchronized oscillation is a propagating calcium wave mediated by Connexin36 (Cx36) gap junctions. A computational islet model predicted that waves emerge due to heterogeneity in β-cell function throughout the islet. To test this, we applied defined patterns of glucose stimulation across the islet using a microfluidic device and measured how these perturbations affect calcium wave propagation.
  • Article

    Systems Mechanobiology: Tension-Inhibited Protein Turnover Is Sufficient to Physically Control Gene Circuits

    • P.C. Dave P. Dingal,
    • Dennis E. Discher
    Mechanotransduction pathways convert forces that stress and strain structures within cells into gene expression levels that impact development, homeostasis, and disease. The levels of some key structural proteins in the nucleus, cytoskeleton, or extracellular matrix have been recently reported to scale with tissue- and cell-level forces or mechanical properties such as stiffness, and so the mathematics of mechanotransduction becomes important to understand. Here, we show that if a given structural protein positively regulates its own gene expression, then stresses need only inhibit degradation of that protein to achieve stable, mechanosensitive gene expression.