{"title":"Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers.","authors":"J P Mills, L Qie, M Dao, C T Lim, S Suresh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force-extension curves, elastic properties and viscoelastic response of human red blood cells subjected to large elastic deformation using optical tweezers. Potential applications of the methods examined here to study diseased cells are also briefly addressed.</p>","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3","pages":"169-80"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26096487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cantilever arrays for multiplexed mechanical analysis of biomolecular reactions.","authors":"Min Yue, Jeanne C Stachowiak, Arunava Majumdar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Microchips containing arrays of cantilever beams have been used to mechanically detect and quantitatively analyze multiple reactions of DNA hybridization and antigen-antibody binding simultaneously. The reaction-induced deflection of a cantilever beam reflects the interplay between strain energy increase of the beam and the free energy reduction of a reaction, providing an ideal tool for investigating the connection between mechanics and chemistry of biomolecular reactions. Since free energy reduction is common for all reactions, the cantilever array forms a universal platform for label-free detection of various specific biomolecular reactions. A few such reactions and their implications in biology and biotechnology are discussed.</p>","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3","pages":"211-20"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26096491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the molecular basis for mechanotransduction.","authors":"Roger D Kamm, Mohammad R Kaazempur-Mofrad","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Much is currently known about the signaling pathways that are excited when cells are subjected to a mechanical stimulus, yet we understand little of the process by which the mechanical perturbation is transformed into a biochemical signal. Numerous theories have been proposed, and each has merit. While cells may possess many different ways of responding to stress, the existence of a single unifying principle has much appeal. Here we propose the hypothesis that cells sense mechanical force through changes in protein conformation, leading to altered binding affinities of proteins, ultimately initiating an intracellular signaling cascade or producing changes in the proteins localized to regions of high stress. More generally, this represents an alternative to transmembrane signaling through receptor-ligand interactions providing the cell with a means of reacting to changes in its mechanical, as opposed to biochemical, environment. One example is presented showing how the binding affinity between the focal adhesion targeting domain of focal adhesion kinase and the LD motif of paxillin is influenced by externally applied force.</p>","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3","pages":"201-9"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26096490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of membrane tension during balloon distension of intestine.","authors":"Hans Gregersen, G. S. Kassab, Yuan-Cheng B. Fung","doi":"10.3970/MCB.2004.001.191","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.191","url":null,"abstract":"During the last decades, it has become increasingly common to make balloons distension in visceral organs in vivo. In particular this is true for studies of gastrointestinal motor function and biomechanics. Balloon distension is often used for assessment of small intestinal compliance and tension based on Laplace's law for cylindrical pressure pipes. This commonly used law is valid only when the balloon-distended intestine is cylindrical. Experimentally, it is seen that the diameter of the balloon-distended intestine is not a constant, but variable in the axial direction. Hence, it is necessary to improve Laplace's law for intestinal investigation. In this paper we develop the framework for determination of the tension distribution in circumferential and longitudinal direction during balloon distension. When the radii of curvature are measured from a photograph of the intestinal profile, then the membrane stress resultants can be computed everywhere in the intestine in contact with the balloon from the equations of equilibrium. The experimental data were obtained from small intestinal segments from five pigs and three guinea pigs. Papaverine was injected before the animals were sacrificed to relax the intestinal smooth muscle. The segments were immersed in a bath with calcium-free Krebs solution with dextran and EGTA. A balloon was distended in the lumen with pressures up to 15 cmH2O in the pigs and 10 cmH2O in the guinea pigs and radii were measured along the z-axis. The tension in circumferential direction had its maximum approximately 25% away from the middle of the balloon. The circumferential tension was 2-3 times higher than the longitudinal tension. In conclusion when we know the shape of the intestine, we can compute the circumferential and longitudinal components of tension. The large variation in tensions along the z axis must be considered when performing balloon distension studies in the gastrointestinal tract for studying physiological and pathophysiological problems in which loading conditions are important, e.g. intestinal mechanoreceptor studies in order to obtain accurate description of the biomechanics and the stimulus-response function.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3 1","pages":"191-9"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70239667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the molecular basis for mechanotransduction.","authors":"R. Kamm, M. Kaazempur-Mofrad","doi":"10.3970/MCB.2004.001.201","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.201","url":null,"abstract":"Much is currently known about the signaling pathways that are excited when cells are subjected to a mechanical stimulus, yet we understand little of the process by which the mechanical perturbation is transformed into a biochemical signal. Numerous theories have been proposed, and each has merit. While cells may possess many different ways of responding to stress, the existence of a single unifying principle has much appeal. Here we propose the hypothesis that cells sense mechanical force through changes in protein conformation, leading to altered binding affinities of proteins, ultimately initiating an intracellular signaling cascade or producing changes in the proteins localized to regions of high stress. More generally, this represents an alternative to transmembrane signaling through receptor-ligand interactions providing the cell with a means of reacting to changes in its mechanical, as opposed to biochemical, environment. One example is presented showing how the binding affinity between the focal adhesion targeting domain of focal adhesion kinase and the LD motif of paxillin is influenced by externally applied force.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3 1","pages":"201-9"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70239778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An improved mathematical approach for determination of molecular kinetics in living cells with FRAP.","authors":"T. Lele, P. Oh, J. Nickerson, D. Ingber","doi":"10.3970/MCB.2004.001.181","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.181","url":null,"abstract":"The estimation of binding constants and diffusion coefficients of molecules that associate with insoluble molecular scaffolds inside living cells and nuclei has been facilitated by the use of Fluorescence Recovery after Photobleaching (FRAP) in conjunction with mathematical modeling. A critical feature unique to FRAP experiments that has been overlooked by past mathematical treatments is the existence of an 'equilibrium constraint': local dynamic equilibrium is not disturbed because photobleaching does not functionally destroy molecules, and hence binding-unbinding proceeds at equilibrium rates. Here we describe an improved mathematical formulation under the equilibrium constraint which provides a more accurate estimate of molecular reaction kinetics within FRAP studies carried out in living cells. Due to incorporation of the equilibrium constraint, the original nonlinear kinetic terms become linear allowing for analytical solution of the transport equations and greatly simplifying the estimation process. Based on mathematical modeling and scaling analysis, two experimental measures are identified that can be used to delineate the rate-limiting step. A comprehensive analysis of the interplay between binding-unbinding and diffusion, and its effect on the recovery curve, are presented. This work may help to bring clarity to the study of molecular dynamics within the structural complexity of living cells.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"288 1","pages":"181-90"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70240062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanmay Lele, Philmo Oh, Jeffrey A Nickerson, Donald E Ingber
{"title":"An improved mathematical approach for determination of molecular kinetics in living cells with FRAP.","authors":"Tanmay Lele, Philmo Oh, Jeffrey A Nickerson, Donald E Ingber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The estimation of binding constants and diffusion coefficients of molecules that associate with insoluble molecular scaffolds inside living cells and nuclei has been facilitated by the use of Fluorescence Recovery after Photobleaching (FRAP) in conjunction with mathematical modeling. A critical feature unique to FRAP experiments that has been overlooked by past mathematical treatments is the existence of an 'equilibrium constraint': local dynamic equilibrium is not disturbed because photobleaching does not functionally destroy molecules, and hence binding-unbinding proceeds at equilibrium rates. Here we describe an improved mathematical formulation under the equilibrium constraint which provides a more accurate estimate of molecular reaction kinetics within FRAP studies carried out in living cells. Due to incorporation of the equilibrium constraint, the original nonlinear kinetic terms become linear allowing for analytical solution of the transport equations and greatly simplifying the estimation process. Based on mathematical modeling and scaling analysis, two experimental measures are identified that can be used to delineate the rate-limiting step. A comprehensive analysis of the interplay between binding-unbinding and diffusion, and its effect on the recovery curve, are presented. This work may help to bring clarity to the study of molecular dynamics within the structural complexity of living cells.</p>","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 3","pages":"181-90"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26096488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. P. Mills, L. Qie, M. Dao, Chwee Teck Lim, S. Suresh
{"title":"Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers.","authors":"J. P. Mills, L. Qie, M. Dao, Chwee Teck Lim, S. Suresh","doi":"10.3970/MCB.2004.001.169","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.169","url":null,"abstract":"Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force-extension curves, elastic properties and viscoelastic response of human red blood cells subjected to large elastic deformation using optical tweezers. Potential applications of the methods examined here to study diseased cells are also briefly addressed.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"152 3 1","pages":"169-80"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70239295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Illuminating the dynamics of intracellular activity with 'active' molecular reporters.","authors":"A Tsourkas, R Weissleder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Traditionally, fluorescent and luminescent reporter proteins have been used as indicators of gene expression and protein localization. However, insightful mutagenesis and protein engineering strategies have transformed these simple passive reporters into active biological sensors. Molecular reporters are now being designed to alter their intrinsic optical properties in response to specific biomolecular interactions. Applications for these novel biological sensors range from monitoring intracellular pH and ion fluxes to detecting protein-protein interactions and enzymatic activity. The ability to monitor the dynamics of intracellular activity in response to external stimuli can help elucidate the cascade of events involved in complex processes such as mechanotransduction. Here we review some of the approaches used to create these novel biological sensors, including resonance energy transfer (RET) between reporter proteins and protein fragmentation strategies.</p>","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 2","pages":"133-45"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26097511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A simple phenomenological theory of tissue growth.","authors":"K. Volokh","doi":"10.3970/MCB.2004.001.147","DOIUrl":"https://doi.org/10.3970/MCB.2004.001.147","url":null,"abstract":"A simple phenomenological framework for modeling growth of living tissues is proposed. Growth is defined as a change of mass and configuration of the tissue. Tissue is considered as an open system where mass conservation is violated and the full-scale mass balance is applied. A possible structure of constitutive equations is discussed with reference to simple growing materials. 'Thermoelastic' formulation of the simple growing material is specified. Within this framework traction free growth of cylindrical and spherical bodies is examined. It is shown that the theory accommodates the case where stresses are not generated in uniform volumetric growth. It is also found that surface growth corresponds to a boundary layer solution of the governing equations. This finding proves the ability of continuum mechanics to describe surface growth. The latter is contrary to the usual use of purely kinematical theories, which do not involve balance and constitutive equations, for treating surface growth.","PeriodicalId":87411,"journal":{"name":"Mechanics & chemistry of biosystems : MCB","volume":"1 2 1","pages":"147-60"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70239461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}