Cell traction force and measurement methods.
03 Jan 2007-Biomechanics and Modeling in Mechanobiology (Springer-Verlag)-Vol. 6, Iss: 6, pp 361-371
TL;DR: Future research should improve CTFM methods such that they can automatically track dynamic CTFs, thereby providing new insights into cell motility in response to altered biological conditions, and research effort should be devoted to developing novel experimental and theoretical methods for determiningCTFs in three-dimensional matrix, which better reflects physiological conditions than 2D substrate used in current CTFm methods.
Abstract: Cell traction forces (CTFs) are crucial to many biological processes such as inflammation, wound healing, angiogenesis, and metastasis. CTFs are generated by actomyosin interactions and actin polymerization and regulated by intracellular proteins such as alpha-smooth muscle actin (alpha-SMA) and soluble factors such as transforming growth factor-beta (TGF-beta). Once transmitted to the extracellular matrix (ECM) through stress fibers via focal adhesions, which are assemblies of ECM proteins, transmembrane receptors, and cytoplasmic structural and signaling proteins (e.g., integrins), CTFs direct many cellular functions, including cell migration, ECM organization, and mechanical signal generation. Various methods have been developed over the years to measure CTFs of both populations of cells and of single cells. At present, cell traction force microscopy (CTFM) is among the most efficient and reliable method for determining CTF field of an entire cell spreading on a two-dimensional (2D) substrate surface. There are currently three CTFM methods, each of which is unique in both how displacement field is extracted from images and how CTFs are subsequently estimated. A detailed review and comparison of these methods are presented. Future research should improve CTFM methods such that they can automatically track dynamic CTFs, thereby providing new insights into cell motility in response to altered biological conditions. In addition, research effort should be devoted to developing novel experimental and theoretical methods for determining CTFs in three-dimensional (3D) matrix, which better reflects physiological conditions than 2D substrate used in current CTFM methods.
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01 Jan 2016
TL;DR: Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells as discussed by the authors, and the potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.
Abstract: Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.
1,837 citations
TL;DR: This review examines the specific physics underlying these phases of cell movement and the origins of the forces that drive locomotion.
Abstract: Cell movement is a complex phenomenon primarily driven by the actin network beneath the cell membrane, and can be divided into three general components: protrusion of the leading edge of the cell, adhesion of the leading edge and deadhesion at the cell body and rear, and cytoskeletal contraction to pull the cell forward. Each of these steps is driven by physical forces generated by unique segments of the cytoskeleton. This review examines the specific physics underlying these phases of cell movement and the origins of the forces that drive locomotion.
454 citations
Cites background from "Cell traction force and measurement..."
...silicone membranes), force sensor arrays and cell traction force microscopy (see Relation Among Force and also recent review [83]) and some of these measurements are shown in Table 2....
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TL;DR: Understanding how forces are generated in these cells and knowing exactly how much force they produce may guide the development of optimal protocols for more effective treatment of tissue wounds in clinical settings.
420 citations
TL;DR: This review of established methods to measure forces generated by cells highlights the technical challenges associated with implementing each technique in a biological laboratory and introduces the established methods.
Abstract: Forces generated by cells are critical regulators of cell adhesion, signaling, and function, and they are also essential drivers in the morphogenetic events of development. Over the past 20 years, several methods have been developed to measure these forces. However, despite recent substantial interest in understanding the contribution of these forces in biology, implementation and adoption of the developed methods by the broader biological community remain challenging because of the inherently multidisciplinary expertise required to conduct and interpret the measurements. In this review, we introduce the established methods and highlight the technical challenges associated with implementing each technique in a biological laboratory.
377 citations
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TL;DR: Fibroblasts are a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
Abstract: Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. Their production of growth factors, chemokines and extracellular matrix facilitates the angiogenic recruitment of endothelial cells and pericytes. Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
4,232 citations
"Cell traction force and measurement..." refers background in this paper
...For example, in tumorigenesis and metastasis, elevated traction force is found in activated fibroblasts (Kalluri and Zeisberg 2006), and transformed cells have lesser traction forces than their non-transformed counterparts (Harris et al....
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TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
3,836 citations