scholarly journals Stiffness Sensing by Cells

2020 ◽  
Vol 100 (2) ◽  
pp. 695-724 ◽  
Author(s):  
Paul A. Janmey ◽  
Daniel A. Fletcher ◽  
Cynthia A. Reinhart-King

Physical stimuli are essential for the function of eukaryotic cells, and changes in physical signals are important elements in normal tissue development as well as in disease initiation and progression. The complexity of physical stimuli and the cellular signals they initiate are as complex as those triggered by chemical signals. One of the most important, and the focus of this review, is the effect of substrate mechanical properties on cell structure and function. The past decade has produced a nearly exponentially increasing number of mechanobiological studies to define how substrate stiffness alters cell biology using both purified systems and intact tissues. Here we attempt to identify common features of mechanosensing in different systems while also highlighting the numerous informative exceptions to what in early studies appeared to be simple rules by which cells respond to mechanical stresses.

1984 ◽  
Vol 246 (2) ◽  
pp. R133-R151 ◽  
Author(s):  
J. S. Clegg

The nucleoplasm, the interiors of cytoplasmic membrane-bound organelles, and the aqueous cytoplasm make up the aqueous compartments of animal cells. The extent to which these compartments are concentrated solutions of macromolecules, metabolites, ions, and other solutes is a matter of some importance to current thinking about cell structure and function. This paper will focus on the aqueous cytoplasm. It will show that the composition and metabolic activities of the cytosol, obtained by methods of cell disruption and fractionation, bear almost no resemblance to those of the aqueous cytoplasm in intact cells. The consequences of this to contemporary views on cell structure and function are considered. A closely related topic concerns the physical properties of the dominant component of these compartments, water: Are these properties the same as those of water in aqueous solutions, or are they altered as a result of interaction with cell architecture? Available evidence strongly suggests that at least a large fraction of the total cell water exhibits properties that markedly differ from those of pure water. Selected examples of these studies will be reviewed, and the roles of cell water will be discussed, notably as they relate to metabolism and cell ultrastructure. Although dimly perceived at present, it appears that living cells exhibit an organization far greater than the current teachings of cell biology reveal.


2010 ◽  
Vol 298 (6) ◽  
pp. C1280-C1290 ◽  
Author(s):  
G. Rickey Welch ◽  
James S. Clegg

Present-day cellular systems biology is producing data on an unprecedented scale. This field has generated a renewed interest in the holistic, “system” character of cell structure-and-function. Underlying the data deluge, however, there is a clear and present need for a historical foundation. The origin of the “system” view of the cell dates to the birth of the protoplasm concept. The 150-year history of the role of “protoplasm” in cell biology is traced. It is found that the “protoplasmic theory,” not the “cell theory,” was the key 19th-century construct that drove the study of the structure-and-function of living cells and set the course for the development of modern cell biology. The evolution of the “protoplasm” picture into the 20th century is examined by looking at controversial issues along the way and culminating in the current views on the role of cytological organization in cellular activities. The relevance of the “protoplasmic theory” to 21st-century cellular systems biology is considered.


2006 ◽  
Vol 01 (04) ◽  
pp. 401-410 ◽  
Author(s):  
PENELOPE C. GEORGES ◽  
ILYA LEVENTAL ◽  
WILFREDO De JESúS ROJAS ◽  
R. TYLER MILLER ◽  
PAUL A. JANMEY

Most biological tissues are soft viscoelastic materials with elastic moduli ranging from approximately 100 to 100,000 Pa. Recent studies have examined the effect of substrate rigidity on cell structure and function, and many, but not all cell types exhibit a strong response to substrate stiffness. Some blood cells such as platelets and neutrophils have indistinguishable structures on hard and soft materials as long as they are sufficiently adhesive, whereas many cell types, including fibroblasts and endothelial cells spread much more strongly on rigid compared to soft substrates. A few cell types such as neurons appear to extend better on very soft materials. The different response of astrocytes and neurons to the stiffness of their substrate results in preferential growth of neurons on soft gels and astrocytes on hard gels, and suggests that preventing rigidification of damaged central nervous system tissue after injury may have utility in wound healing. How cells sense substrate stiffness is unknown. One candidate protein, filamin A, which responds to externally derived stresses, was tested in melanoma cells. Cells devoid of filamin A retain the ability to sense substrate stiffness, suggesting that other proteins are required for stiffness sensing.


2009 ◽  
Vol 60-61 ◽  
pp. 27-30 ◽  
Author(s):  
Li Ping Liu ◽  
Yun Dou Wang ◽  
Yan Jun Zhang

In cell biology and medicine study, continuous high spatial resolution observations of living cells would greatly aid the elucidation of the relationship between structure and function of cells. The development of scanning probe microscopy (SPM) has opened up a new era of life science and has been used to develop a family of related methods that allow studying of cell structure and function on nanometer scale. Scanning ion conductance microscopy (SICM) is a new member of such SPM family and can be used to obtain high-resolution non-contact images of the surface of live cells under physiological conditions, and hence allows the relationship between cell microstructure and function to be probed. In this review, we concisely introduce the principles of SICM and its applications in nanobiology and nanomedicine.


1993 ◽  
Vol 115 (4B) ◽  
pp. 510-514 ◽  
Author(s):  
Robert M. Nerem

The endothelium, once thought to be a passive, non-thrombogenic barrier, is now recognized as being a dynamic participant in vascular biology and pathobiology. Part of its dynamic nature is due to the influence of the mechanical environment imposed by the hemodynamics of the vascular system. Over the past two decades much has been learned about the influence of hemodynamics on the vascular endothelium. This has been in part through in vivo experiments; however, in the past 15 years a number of laboratories have turned to the application of in vitro cell culture systems to investigate the influence of flow and cyclic stretch on the biology of vascular endothelium. Taken together these studies demonstrate that flow and the associated shear stress modulate both endothelial cell structure and function. Cell culture studies employing cyclic stretch provide similar evidence. Furthermore, these effects of mechanical environment extend to the gene expression level, with there being a differential regulation of mRNA. A critical question is how does an endothelial cell recognize the mechanical environment in which it resides and, having done so, how is this transduced into the changes in structure and function observed? Although our knowledge of the recognition events remains limited, studies on signal transduction in response to a mechanical stimulus indicate that many of the second messengers known to be triggered by chemical agonists also are involved in transducing a mechanical signal. Over the past 20 years our understanding of the importance of the influence of the mechanical environment imposed by the hemodynamics of the system on vascular endothelial biology, both in the regulation of the normal biology of blood vessels and as a determinant of the distribution and development of atherosclerotic lesions, has grown immensely; however, there is still much to be learned.


2001 ◽  
Vol 114 (15) ◽  
pp. 2723-2733 ◽  
Author(s):  
Paul G. McKean ◽  
Sue Vaughan ◽  
Keith Gull

Although most eukaryotic cells can express multiple isotypes of αβ-tubulin, the significance of this diversity has not always been apparent. Recent data indicate that particular αβ-tubulin isotypes, both genome encoded and those derived by post-translational modification, can directly influence microtubule structure and function — thus validating ideas originally proposed in the multitubulin hypothesis over 25 years ago.It has also become increasingly evident over the past year that some (but intriguingly not all) eukaryotes encode several other tubulin proteins, and to date five further members of the tubulin superfamily, γ, δ, ϵ, 𝛇 and η, have been identified. Although the role of γ-tubulin in the nucleation of microtubule assembly is now well established, far less is known about the functions of δ-, ϵ-, 𝛇- and η-tubulin. Recent work has expanded our knowledge of the functions and localisation of these newer members of the tubulin superfamily, and the emerging data suggesting a restricted evolutionary distribution of these `new' tubulin proteins, conforms to established knowledge of microtubule cell biology. On the basis of current evidence, we predict that δ-, ϵ-, 𝛇- and η-tubulin all have functions associated with the centriole or basal body of eukaryotic cells and organisms.


Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.


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