An Emerging Field Between Biology and Biomechanics
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Protein Cell DOI 10.1007/s13238-014-0057-9 Protein & Cell REVIEW Mechanomics: an emerging field between biology and biomechanics Jiawen Wang, Dongyuan Lü, Debin Mao, Mian Long& Center for Biomechanics and Bioengineering and Key Laboratory of Microgravity, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China & Correspondence: [email protected] (M. Long) Received January 6, 2014 Accepted March 10, 2014 Cell ABSTRACT INTRODUCTION & Cells sense various in vivo mechanical stimuli, which Mechanical stimuli are crucial to many biological processes at initiate downstream signaling to mechanical forces. organ, tissue, cell, and molecule levels. Shear flow, tensile While a body of evidences is presented on the impact of stretch, and mechanical compression are most typical in vivo limited mechanical regulators in past decades, the mechanical stimuli, which are in action alone or synergistically mechanisms how biomechanical responses globally with other mechanical and even biochemical factors (Wang, Protein affect cell function need to be addressed. Complexity 2006; Cohen and Chen, 2008). For example, endothelial cells and diversity of in vivo mechanical clues present dis- are subjected to blood shear flow and orientated towards the tinct patterns of shear flow, tensile stretch, or mechan- flow direction (Silkworth and Stehbens, 1975), extracellular ical compression with various parametric combination matrices (ECMs) are stretched to mediate the outside-in sig- of its magnitude, duration, or frequency. Thus, it is naling (Wright et al., 1997), and cartilage tissue is compressed required to understand, from the viewpoint of me- to initiate interstitial fluid pressurization (Soltz and Ateshian, chanobiology, what mechanical features of cells are, 2000). A body of cues is known about how these mechanical why mechanical properties are different among distinct stimuli affect cell morphology, proliferation, and differentiation. cell types, and how forces are transduced to down- Evidently, it is difficult to elucidate what really happen at cellular stream biochemical signals. Meanwhile, those in vitro and molecular levels if only a single type of mechanical stimuli isolated mechanical stimuli are usually coupled together or one set of mechanical parameters at a given stimulus is used. in vivo, suggesting that the different factors that are in Homeostatic imbalances are main driving forces to initiate effect individually could be canceled out or orchestrated physiological changes, in which various stimuli are moni- with each other. Evidently, omics analysis, a powerful tored closely by receptors and sensors at different sites. tool in the field of system biology, is advantageous to Most of mechanoreceptors often react to shear flow, tensile combine with mechanobiology and then to map the full- stretch, or mechanical compression. When multiple mechan- set of mechanically sensitive proteins and transcripts ical stimuli or parameters are pooled together, part(s) of encoded by its genome. This new emerging field, those molecular events presented in individual stimuli tests namely mechanomics, makes it possible to elucidate the might be reserved constantly, fostered cooperatively, or global responses under systematically-varied mechani- canceled out each other, since the cross-talks existing in the cal stimuli. This review discusses the current advances mechanically sensitive genes and proteins would exert null, in the related fields of mechanomics and elaborates how synergistic, or opposite effects. Thus, global mapping of cells sense external forces and activate the biological activated genes and proteins that are responsible to the responses. specific mechanical stimuli is required to conduct from the viewpoint of omics. In this review, cellular and molecular KEYWORDS mechanomics, mechanobiology, responses to mechanical stimuli were discussed, and the proteomics, transcriptomics new conceptual terminology of mechanomics referred to © The Author(s) 2014. This article is published with open access at Springerlink.com and journal.hep.com.cn REVIEW Jiawen Wang et al. A High on the magnitude, frequency, and duration of mechanical Cell 1 forces. On the other hand, omics is the most striking tool to globally map the cellular and molecular responses to various bio- Cell 2 Low chemical and biomechanical stimuli. It aims, from the viewpoint F of system biology, at the characterization and quantification of Cell 3 pooled biological molecules that transmit external signals to alter the structure, function, and dynamics of an organism or organisms. Integration of existing approaches in biomechanics and high-throughput transcriptomics/proteomics enables us to ••• Cell 5Cell 8 Cell 6Cell 4Cell 7Cell 3Cell 2Cell 1Cell 9 profile cell phenotype under complicated mechanical stimuli Cell 10 High B and to elucidate the mechanisms in cell type-specificme- F1 chanobiology (Davies et al., 2005). Current efforts mainly focus on understanding the transcriptomics/proteomics on the pat- Low tern or parametric dependence of one specifictypeoronthe F2 combined types in respective pattern or parameter sets. Here we discuss the combination of these two fields along typical mechanical clues where the detailed parameters are summa- F3 rized in Table 1 for clarity. Cell ••• F10 F8 F7 F4 F5 F6 F3 F1 F9 F2 & Figure 1. Schematic of cellular responses to mechanical Mechanical modeling of a cell stimuli in one-to-more (A) or more-to-one pattern (B). Each Cells sense their mechanical environment, which, in turn, row of the heatmap represents different genes, of which the regulates their functions. Various theoretical models are pro- abundance is indicated by top-right color key, and each column posed to understand mechanical regulation of cell functions, Protein of the heatmap denotes distinct cells (A) and different mechan- which provide differential mathematical solutions. At subcel- ical forces (B). lular level, most models are attempting to predict the force or stress distribution of cytoskeletal network and mimic the transcriptomics and proteomics combined with systemati- remodeling of mechanically sensitive cytoskeletal proteins cally-varied mechanical stimuli was proposed. (Ingber, 1997; Li, 2008; Geiger et al., 2009). At cellular level, a cell is usually modeled as an encapsulated lipid membrane containing stress-supported structures to support its defor- MECHANOBIOLOGY AND TRANSCRIPTOMICS/ mation, adhesion, and spreading (Evans and Yeung, 1989; PROTEOMICS Stamenovic and Ingber, 2002; Murrell et al., 2011). At tissue Mechanobiology is an interdisciplinary field at the interface of level, mathematically models are developed to predict the mechanics and biology that emerges over last two decades dynamics of tumor growth (Chaplain et al., 2006) and osteo- (Wang et al., 2008). It focuses on elucidating the mecha- genic differentiation (Carter et al., 1998) under mechanical nisms how external forces or changes in cell or tissue stimuli. These models also help to elucidate the mechanisms mechanical environment contribute to development, physi- how cells resist shape distortion and maintain their structural ology, and disease of an organism. A major challenge in this stability and how they convert mechanical signals into bio- field is to elucidate the molecular mechanisms of mecha- chemical responses. Regardless of their advantages in the- notransduction, by which cells sense and respond to bio- oretical prediction, these models are still required to compare mechanical signals and convert them into biochemical with the relevant experimental measurements. signals (Katsumi et al., 2004; Long et al., 2011; Dado et al., 2012). Numerous mechanoreceptors, such as ECM mole- Single type of mechanical stimuli cules, transmembrane proteins, cytoskeleton, nuclei, and Current works on mechanobiology and mechanotransduc- lipid bilayer, are mechanically sensitive and then initiate tion are mainly focused on understanding how the cells inside-out or outside-in mechanotransduction for cells (Jan- sense and respond to a single type of mechanical stimuli and mey and McCulloch, 2007). A single type of mechanical what the functional molecules are only on the basis of a few stimuli in vitro often provokes cell’s sensing and responding protein effectors. to external forces via multiple molecular events (Fig. 1A). By contrast, multiple types of mechanical stimuli are present Shear flow around a cell or cells in vivo and act on the cell(s) synergis- tically (Fig. 1B). It is also noticed that the physiological stimuli Cellular responses to shear flow that mimics the physiolog- are usually dynamic rather than static, which highly depends ical blood or interstitial flow are extensively investigated © The Author(s) 2014. This article is published with open access at Springerlink.com and journal.hep.com.cn © Mechanomics between biology and biomechanics The Author(s) 2014. This article is published with open access at Springerlink.comTable and journal.hep.com.cn 1. Summaries of mechanotransduction under typical mechanical stimuli Stimuli Types Pattern Parameters Acting cells/tissues Related molecules References Shear flow Isolated Laminar/steady 10–20 dyne/cm2,3–24 h ECs Integrins, Flk-1, GPCRs, Li et al. (2005) PECAM-1 12 dyne/cm2, 24 h ECs Tie2, Flk-1, MMP1 Chen et al. (2001) 5–15 dyne/cm2, 24 h ECs PDGF-BB, TGF-β1, Lamin A Qi et al. (2011) 15 dyne/cm2,0–6 h ECs PKA, PECAM-1, VEGFR2 Wang et al. (2009) 12 dyne/cm2,4–24 h ECs, SMCs ICAM-1 Heydarkhan-Hagvall et al. (2006) 3 dyne/cm2, 6 h MSCs Annexin, GAPDH Yi