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#mechanical

24 Beiträge15 Beteiligte7 Beiträge heute

📰 "Optogenetic control of mechanotransduction based on light-induced homodimerization of talin"
biorxiv.org/content/10.1101/20 #Mechanotransduction #Mechanical #Cell

bioRxiv · Optogenetic control of mechanotransduction based on light-induced homodimerization of talinIntegrin-based cell adhesions (IACs) serve as primary sites where piconewton-scale actomyosin-generated mechanical forces are transmitted to the extracellular matrix (ECM), generating traction forces that drive cell-ECM responses including adhesion, migration, and mechano-signaling. Talin, a large (270 kDa) cytosolic adaptor protein, is the principal force-transmission protein in integrin-based adhesions, containing multiple mechanosensitive domains and protein-protein interaction sites that orchestrate molecular events in mechanosensing. As a highly modular multi-domain protein, talin has been identified as an effective target for chemogenetic and optogenetic manipulation of integrin-based mechanotransduction. However, a key limitation of previous approaches is the reliance on heterodimerization modules to control talin function, requiring the expression of two modified talin fragments. In practice, achieving precise expression levels in such a 2-component approach can be challenging, particularly when combined with other genetic tools. Since talin naturally contains a C-terminal dimerization domain that forms part of its actin-binding site, we reasoned that the molecularly engineered talin with a C-terminal optically-controlled homodimerizer could enable single-component optogenetic control of mechanotransduction. This approach would facilitate multiplexing with other molecular perturbations or experimental techniques. Here, we describe an opto-homodimerizable talin based on the pdDronpa1.2 optogenetic module, which enables optogenetic control of talin by a single construct. We demonstrate that light-induced talin dimerization promotes talin recruitment to IACs, adhesion formation, actin retrograde flow engagement, and downstream mechanotransduction signaling. Conversely, light-induced talin monomerization rapidly disassembles focal adhesions, disrupts talin-actin linkages, and accelerates actin retrograde flow, underscoring the critical roles of talin dimerization. Furthermore, our single-construct design allows facile multiplexing of optogenetic modulation of integrin-mediated mechanotransduction with super-resolution single-molecule tracking, revealing the essential role of talin dimerization for integrin αvβ5 engagement. ### Competing Interest Statement The authors have declared no competing interest.

📰 "Mechanical cues rewire lipid metabolism and support chemoresistance in epithelial ovarian cancer cell lines OVCAR3 and SKOV3"
doi.org/doi:10.1186/s12964-025
pubmed.ncbi.nlm.nih.gov/402642
#Mechanical #Cell

BioMed CentralMechanical cues rewire lipid metabolism and support chemoresistance in epithelial ovarian cancer cell lines OVCAR3 and SKOV3 - Cell Communication and SignalingEpithelial ovarian cancer (EOC) is one of the deadliest cancers in women, and acquired chemoresistance is a major contributor of aggressive phenotypes. Overcoming treatment failure and disease recurrence is therefore an ambitious goal. Ovarian cancer develops in a biophysically challenging environment where the cells are constantly exposed to mechanical deformation originating in the abdomen and shear stress caused by the accumulation of ascitic fluid in the peritoneal cavity. Therefore, mechanical stimulation can be seen as an inseparable part of the tumor microenvironment. The role of biomechanics in shaping tumor metabolism is emerging and promises to be a real game changer in the field of cancer biology. Focusing on two different epithelial ovarian cancer cell lines (SKOV3 and OVCAR3), we explored the impact of shear stress on cellular behavior driven by mechanosensitive transcription factors (TFs). Here, we report data linking physical triggers to the alteration of lipid metabolism, ultimately supporting increased chemoresistance. Mechanistically, shear stress induced adaptation of cell membrane and actin cytoskeleton which were accompanied by the regulation of nuclear translocation of SREBP2 and YAP1. This was associated with increased cholesterol uptake/biosynthesis and decreased sensitivity to the ruthenium-based anticancer drug BOLD-100. Overall, the present study contributes to shedding light on the molecular pathways connecting mechanical cues, tumor metabolism and drug responsiveness.

New rules in the machining industry: CNC operators must be beautiful?
——
The truth is... only GreatLight has a 'machine goddess'!

0.001mm error engraving makes the machine more 'obedient' than your girlfriend!

⚠️ Be careful, colleagues! I'm afraid that the masters in your factory will collectively change jobs...
#CNC romance #Happiness of machine operators #Mechanical girlfriend #Industrial hard work #CNC love story

👉 Click to see the real record of 'beauties' working overtime late at night

📰 "Curvature induced patterns: A geometric, analytical approach to understanding a mechanochemical model"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Curvature induced patterns: A geometric, analytical approach to understanding a mechanochemical modelThe exact mechanisms behind many morphogenic processes are still a mystery. Mechanical cues, such as curvature, play an important role when tissue or cell shape is formed. In this work, we derive and analyze a mechanochemical model. This particular spatially one-dimensional model describes the deformation of a tissue- or cell surface over time, which is driven by a morphogen that locally induces curvature. The model consists of two PDEs with periodic boundary conditions; one reaction-diffusion equation for the morphogen and one PDE that describes the dynamics of the curve, derived by taking the L2-gradient flow of the Helfrich energy. We analyze the possible steady states of this model using geometric singular perturbation theory. It turns out that the strength of interaction between the morphogen and the curvature plays a key role in the type of possible steady state solutions. In the case of weak interaction, the geometry of the slow manifolds allows only for (in space) slowly changing periodic orbits that lay completely on one slow manifold. In the case of strong interaction, there exist multiple front solutions: periodic orbits that jump between different slow manifolds. The singular skeletons of the steady state solutions do not meet the required consistency conditions for the curvature, a priori indicating that the solutions might not be observable. The observability and stability are investigated further using numerical simulation. ### Competing Interest Statement The authors have declared no competing interest.

Right as we speak a copy of one of my large audio projects is made to a mechanical HDD. I ask myself why technology has not evolved in a way that single consumer grade drives can take the TB of data they hold in at speeds that are proportional to their size.

It takes 10 minutes for a puny 100GB to be transferred at about 160MB/s from the M.2 SSD to the mechanical spinner which still rotates at that lousy 7200RPM.

My Ultrawide SCSI Fijitsu HDD on my A4000T rotated at 10.000RPM! That HDD is from the last century!!!

IT still works!

If HDD companies put in the proper research we may not be having 20.000RPM drives on servers, because of mechanical limits, but we should have had 10.000 rpm drives now for consumer grade mechanical HDDs.

#Data#Backup#Amiga