Measuring cellular traction forces on non-planar substrates

Soiné, Jérôme R. D.; Hersch, Nils; Dreissen, Georg; Hampe, Nico; Hoffmann, Bernd; Merkel, Rudolf; Schwarz, Ulrich S.

doi:10.1098/rsfs.2016.0024

Cited by 20 publications

(14 citation statements)

References 71 publications

(89 reference statements)

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“…However, as discussed in Sect. 15.3 of this chapter, recent advancements are beginning to reduce the need to rely on such assumptions [38][39][40][41][42]. Certain traction force reconstruction methods also rely on additional imaging data, typically in the form of cell structural information, such as a cell membrane outline, or the location of focal adhesion sites [27,[43][44][45].…”

Section: From Engineered Systems To Cell Forcesmentioning

confidence: 99%

Traction Force Microscopy for Noninvasive Imaging of Cell Forces

Mulligan

Bordeleau

Reinhart‐King

et al. 2018

Advances in Experimental Medicine and Biology

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The forces exerted by cells on their surroundings play an integral role in both physiological processes and disease progression. Traction force microscopy is a noninvasive technique that enables the in vitro imaging and quantification of cell forces. Utilizing expertise from a variety of disciplines, recent developments in traction force microscopy are enhancing the study of cell forces in physiologically relevant model systems, and hold promise for further advancing knowledge in mechanobiology. In this chapter, we discuss the methods, capabilities, and limitations of modern approaches for traction force microscopy, and highlight ongoing efforts and challenges underlying future innovations.

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Section: From Engineered Systems To Cell Forcesmentioning

confidence: 99%

Traction Force Microscopy for Noninvasive Imaging of Cell Forces

Mulligan

Bordeleau

Reinhart‐King

et al. 2018

Advances in Experimental Medicine and Biology

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“…We measured contractility as an indicator of cardiomyocyte function, but another key functional measurement is the traction forces the cell exerts on the substrate as it contracts. While this technique has been well-refined for cells on planar surfaces, it is still being developed for cells on three-dimensional substrates (57). Non-planar substrates lead to large error in the z direction with variable point spread functions, making reliable analysis with typical equipment difficult.…”

Section: Discussionmentioning

confidence: 99%

Cardiac myocytes respond differentially and synergistically to matrix stiffness and topography

Wan

Bjorkman

Choi

et al. 2019

Preprint

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During cardiac disease progression, myocytes undergo molecular, functional and structural changes, including increases in cell size and shape, decreased myocyte alignment and contractility. The heart often increases extracellular matrix production and stiffness, which affect myocytes. The order and hierarchy of these events remain unclear as available in vitro cell culture systems do not adequately model both physiologic and pathologic environments. Traditional cell culture substrates are 5-6 orders of magnitude stiffer than even diseased native cardiac tissue. Studies that do account for substrate stiffness often do not consider intercellular alignment and vice versa. We developed a cardiac myocyte culture platform that better recapitulates native tissue stiffness while simultaneously introducing topographical cues that promote cellular alignment. We show that stiffness and topography impact myocyte molecular and functional properties. We used a spatiotemporally-tunable, photolabile hydrogel platform to generate a range of stiffness and micron-scale topographical patterns to guide neonatal rat ventricular myocyte morphology. Importantly, these substrate patterns were of subcellular dimensions to test whether cells would spontaneously respond to topographical cues rather than an imposed geometry. Cellular contractility was highest and the gene expression profile was most physiologic on gels with healthy cardiac tissue stiffness. Surprisingly, while elongated patterns in stiff gels yielded the greatest cellular alignment, the cells actually had more pathologic functional and molecular profiles. These results highlight that morphological measurements alone are not a surrogate for overall cellular health as many studies assume. In general, substrate stiffness and micropatterning synergistically affect cardiac myocyte phenotype to recreate physiologic and pathologic microenvironments.Significance StatementHeart disease is accompanied by organ- and cellular-level remodeling, and deconvoluting their interplay is complex. Cellular-level change is best studied in vitro due to greater control and uniformity of cell types compared to animals. One common metric is degree of cellular alignment as misalignment of myocytes is a hallmark of disease. However, most studies utilize featureless culture surfaces that are orders of magnitude stiffer than, and do not mimic the scaffolding of, the heart. We developed a hydrogel platform with tunable stiffness and patterns providing topographical alignment cues. We cultured heart cells on and characterized multifactorial responses to these dynamic surfaces. Interestingly, conditions that yielded greatest alignment did not yield the healthiest functional and molecular state. Thus, morphology alone is not an indicator of overall cellular health.

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“…3D environments invalidate this assumption and therefore require thorough characterization of the interface between the cell surface and the underlying substrate (i.e., approximations of surface normals). While this approach has been accomplished for isolated cells embedded in hydrogels or on nonplanar surfaces, [ 159,162 ] it needs to be adapted to incorporate the additional complexity of vascularized networks (Figure 2).…”

Section: Measuring Cell and Tissue Mechanical Properties For Mechanotmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Measuring cellular traction forces on non-planar substrates

Cited by 20 publications

References 71 publications

Traction Force Microscopy for Noninvasive Imaging of Cell Forces

Traction Force Microscopy for Noninvasive Imaging of Cell Forces

Cardiac myocytes respond differentially and synergistically to matrix stiffness and topography

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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