Protein nanomechanics in biological context.

How proteins respond to pulling forces, or protein nanomechanics, is a key contributor to the form and function of biological systems. 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. These tethered proteins typically have important mechanical roles that enable cells to generate, sense, and transduce mechanical forces. To fully comprehend the interplay between mechanical forces and biology, we must understand how protein nanomechanics emerge in living matter. This endeavor is definitely challenging and only recently has it started to appear tractable. Here, I introduce the main in vitro single-molecule biophysics methods that have been instrumental to investigate protein nanomechanics over the last 2 decades. 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. 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. Finally, I discuss emerging methods to modulate protein nanomechanics in living matter, for instance by inducing specific mechanical loss-of-function (mLOF). By interrogating biological systems in a causative manner, these new tools can contribute to further place protein nanomechanics in a biological context.We have received funding from the Ministerio de Ciencia e Innovación through grant EIN2019-102966 and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. [101002927]) to develop mechanical loss-of-function tools.S

How to get to build your own lab

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From single molecules to heart disease

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Los problemas morales en la investigación científica

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Protein Hydrogels: The Swiss Army Knife for Enhanced Mechanical and Bioactive Properties of Biomaterials.

Biomaterials are dynamic tools with many applications: from the primitive use of bone and wood in the replacement of lost limbs and body parts, to the refined involvement of smart and responsive biomaterials in modern medicine and biomedical sciences. Hydrogels constitute a subtype of biomaterials built from water-swollen polymer networks. Their large water content and soft mechanical properties are highly similar to most biological tissues, making them ideal for tissue engineering and biomedical applications. The mechanical properties of hydrogels and their modulation have attracted a lot of attention from the field of mechanobiology. Protein-based hydrogels are becoming increasingly attractive due to their endless design options and array of functionalities, as well as their responsiveness to stimuli. Furthermore, just like the extracellular matrix, they are inherently viscoelastic in part due to mechanical unfolding/refolding transitions of folded protein domains. This review summarizes different natural and engineered protein hydrogels focusing on different strategies followed to modulate their mechanical properties. Applications of mechanically tunable protein-based hydrogels in drug delivery, tissue engineering and mechanobiology are discussed.We acknowledges funding from the Ministerio de Ciencia e Innovación (MCIN) through grant BIO2017-83640-P (AEI/FEDER, UE), RYC-2014-16604, and the Comunidad de Madrid (consortium Tec4Bio-CM, S2018/NMT-4443, FEDER). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIN and the Pro CNIC Foundation, and was a Severo Ochoa Center of Excellence (SEV-2015-0505). CHL was the recipient of an FPI predoctoral fellowship (BES-2015-073191).S

Técnicas de molécula individual aplicadas al estudio de proteínas

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Correspondence on "Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation" by Thompson et al.

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The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C.

Hypertrophic cardiomyopathy (HCM), a disease characterized by cardiac muscle hypertrophy and hypercontractility, is the most frequently inherited disorder of the heart. HCM is mainly caused by variants in genes encoding proteins of the sarcomere, the basic contractile unit of cardiomyocytes. The most frequently mutated among them is MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), a key regulator of sarcomere contraction. In this review, we summarize clinical and genetic aspects of HCM and provide updated information on the function of the healthy and HCM sarcomere, as well as on emerging therapeutic options targeting sarcomere mechanical activity. Building on what is known about cMyBP-C activity, we examine different pathogenicity drivers by which MYBPC3 variants can cause disease, focussing on protein haploinsufficiency as a common pathomechanism also in nontruncating variants. Finally, we discuss recent evidence correlating altered cMyBP-C mechanical properties with HCM development.Research in our laboratory on HCM pathomechanisms induced by MYBPC3 variants is funded by the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) through grant PID2020120426GB-I00 and the Severo Ochoa Program for Centers of Excellence in R&D in its 2015 and 2020 calls (ref. SEV-2015-0505 and ref. CEX2020-001041-S); and by consortium Tec4Bio-CM (S2018/NMT-4443) from the Comunidad de Madrid. This last call is 50% co-financed by the European Social Fund (ESF) and the European Regional Development Fund (ERDF) for the programming period 2014-2020. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIN and the Pro CNIC Foundation. CS-C is the recipient of an FPI-SO predoctoral fellowship BES-2016-076638. We thank Eli ' as Herrero-Gal ' an for critical feedback. We thank Metello Innocenti for editorial feedback. We thank two anonymous reviewers for their expert feedback.N

Irreproducibility in Research. What can we do about it?

We all would agree with Karl Popper's statement: 'Non-reproducible single occurrences are of no significance to science.' But what if a substantial percentage of published scientific facts are of the irreproducible category? Such an alarming scenario may be close to reality, according to a number of recent reports. Indeed, some shocking statistics suggest that irreproducibility has gone awry in the last years. For instance, pharma and biotech companies can only reproduce between 11 and 25% high-impact research papers in the field of cancer research