Mechano-transduction: from molecules to tissues.

External forces play complex roles in cell organization, fate, and homeostasis. Changes in these forces, or how cells respond to them, can result in abnormal embryonic development and diseases in adults. How cells sense and respond to these mechanical stimuli requires an understanding of the biophysical principles that underlie changes in protein conformation and result in alterations in the organization and function of cells and tissues. Here, we discuss mechano-transduction as it applies to protein conformation, cellular organization, and multi-cell (tissue) function

Micro- and nanoengineering approaches to control stem cell-biomaterial interactions.

As our population ages, there is a greater need for a suitable supply of engineered tissues to address a range of debilitating ailments. Stem cell based therapies are envisioned to meet this emerging need. Despite significant progress in controlling stem cell differentiation, it is still difficult to engineer human tissue constructs for transplantation. Recent advances in micro- and nanofabrication techniques have enabled the design of more biomimetic biomaterials that may be used to direct the fate of stem cells. These biomaterials could have a significant impact on the next generation of stem cell based therapies. Here, we highlight the recent progress made by micro- and nanoengineering techniques in the biomaterials field in the context of directing stem cell differentiation. Particular attention is given to the effect of surface topography, chemistry, mechanics and micro- and nanopatterns on the differentiation of embryonic, mesenchymal and neural stem cells

Heading in the right direction : guiding cellular alignment by substrate anisotropy

Energie en entropie sturen cellen in de zelfde richtin

Biophysical regulation of stem cell behavior within the niche.

Stem cells reside within most tissues throughout the lifetimes of mammalian organisms. To maintain their capacities for division and differentiation and thereby build, maintain, and regenerate organ structure and function, these cells require extensive and precise regulation, and a critical facet of this control is the local environment or niche surrounding the cell. It is well known that soluble biochemical signals play important roles within such niches, and a number of biophysical aspects of the microenvironment, including mechanical cues and spatiotemporally varying biochemical signals, have also been increasingly recognized to contribute to the repertoire of stimuli that regulate various stem cells in various tissues of both vertebrates and invertebrates. For example, biochemical factors immobilized to the extracellular matrix or the surface of neighboring cells can be spatially organized in their placement. Furthermore, the extracellular matrix provides mechanical support and regulatory information, such as its elastic modulus and interfacial topography, which modulate key aspects of stem cell behavior. Numerous examples of each of these modes of regulation indicate that biophysical aspects of the niche must be appreciated and studied in conjunction with its biochemical properties

Directed cell migration in multi-cue environments

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing and cancer metastasis. During these processes, cells are often directed to migrate towards targets by sensing aligned fibers or gradients in concentration, mechanical properties or electric field. Often times, cells must integrate migrational information from several of these different cues. While the cell migration behavior, signal transduction and cytoskeleton dynamics elicited by individual directional cues has been largely determined, responses to multiple directional cues are much less understood. However, initial work has pointed to several interesting behaviors in multi-cue environments, including competition and cooperation between cues to determine the migrational responses of cells. Much of the work on multi-cue sensing has been driven by the recent development of approaches to systematically and simultaneously control directional cues in vitro coupled with analysis and modeling that quantitatively describe those responses. In this review we present an overview of multi-cue directed migration with an emphasis on how cues compete or cooperate. We outline how multi-cue responses such as cue dominance might change depending on other environmental inputs. Finally, the challenges associated with the design of the environments to control multiple cues and the analysis and modeling of cell migration in multi-cue environments as well as some interesting biological questions associated with migration in complex environments are discussed. Understanding multi-cue migrational responses is critical to the mechanistic description of physiology and pathology, but also to the design of engineered tissues, where cell migration must be orchestrated to form specific tissue structures