Lisett rodriguez galan girls with muscle
For over 2 decades, and using different single-molecule approaches, the protein nanomechanics field has gathered extensive information on how force affects the conformational dynamics of proteins.
This review focuses on the behavior of proteins under force, or protein nanomechanics, which is relevant not only to understanding protein-based mechanosensing but also organelle integrity, cell adhesion, and muscle function (Figure 1). 2009 Douguet and Honoré 2019 Echarri et al. Several molecular mechanisms contribute to mechanosensing and mechanotransduction, including membrane tension sensing by mechanosensitive ion channels, flow sensing by extracellular mechanosensors, modulation of the actomyosin cytoskeleton, and force sensing by load-bearing, tethered proteins (del Rio et al. 2019 Hannezo and Heisenberg 2019 Matamoro-Vidal and Levayer 2019 Roca-Cusachs et al. The evolving view is that the landscape of force sensing and force generation mechanisms by cells is broad, highlighting the fact that cells have to ensure correct processing and integration of different mechanical signals for optimal fitness, proliferation, differentiation, and migration (De Pascalis and Etienne-Manneville 2017 Echarri et al. 2017), and nano- and microfabrication of cell substrates with controlled geometries and their integration into microfluidics platforms for 2D and 3D cell culture (Castiaux et al. 2019) and molecular (Neuman and Nagy 2008) levels, tools to probe cell mechanics (Roca-Cusachs et al. These new insights have been enabled by several technological developments, including production of cell-culture-compatible hydrogels with tunable mechanical properties (Caliari and Burdick 2016), force-sensing methods at the cellular (Cost et al. 2016), and that during some bacterial infections, the fight between host and pathogen is mainly mechanical (Persat et al. 2018), that gene expression depends on the mechanics of the nucleus (Shin et al. 2017), that changes in cell and tissue mechanics are important for the onset and evolution of diseases like cancer (Broders-Bondon et al.
2006), that mechanical forces are fundamental for development (Mammoto et al. These include the observation that stem cell differentiation is determined by the stiffness of the extracellular matrix (ECM) (Engler et al. The field of mechanobiology, which is concerned with the study of mechanical forces in biology at the molecular, cellular, and organismal scales, has already led to several paradigm shifts. The interplay between mechanical forces and biology involves processes of active force generation by cells but also dedicated mechanisms that sense (mechanosensing) and translate (mechanotransduction) mechanical forces into the language of the cell, which is written in biochemical and metabolic words (Saucerman et al. 2019), and cardiac hypertrophy due to elevated blood pressure (Drazner 2011). 2010), brain damage caused by concussion events (Hirad et al. Classical examples include muscle atrophy induced by long-duration spaceflights (Fitts et al. By interrogating biological systems in a causative manner, these new tools can contribute to further place protein nanomechanics in a biological context.īiological systems generate and respond to mechanical forces, determining cell and tissue behavior in health and disease (Guck 2019 Hannezo and Heisenberg 2019 Matamoro-Vidal and Levayer 2019 Roca-Cusachs et al. Finally, I discuss emerging methods to modulate protein nanomechanics in living matter, for instance by inducing specific mechanical loss-of-function (mLOF). To illustrate the contribution of protein nanomechanics to biological function, I review current knowledge on the mechanobiology of selected muscle and cell adhesion proteins including titin, talin, and bacterial pilins.
#Lisett rodriguez galan girls with muscle free#
Then, I present the contemporary view on how mechanical force shapes the free energy of tethered proteins, as well as the effect of biological factors such as post-translational modifications and mutations. Here, I introduce the main in vitro single-molecule biophysics methods that have been instrumental to investigate protein nanomechanics over the last 2 decades. This endeavor is definitely challenging and only recently has it started to appear tractable.
To fully comprehend the interplay between mechanical forces and biology, we must understand how protein nanomechanics emerge in living matter. These tethered proteins typically have important mechanical roles that enable cells to generate, sense, and transduce mechanical forces. Indeed, the conventional view that proteins are able to diffuse in solution does not apply to the many polypeptides that are anchored to rigid supramolecular structures. How proteins respond to pulling forces, or protein nanomechanics, is a key contributor to the form and function of biological systems.