|1||Actin filament assembly |
Source: http://www.mechanobio.info/modules/go-0030041 (Mechanobiology Institute, Singapore). The actin network is made up of filamentous actin (F-actin). These filaments are highly dynamic in nature and comprise monomers of G-actin bound to either ATP (yellow) or ADP (blue). Assembly is powered by ATP hydrolysis and filament nucleation happens spontaneously in vitro. Polymerization: Addition of ATP-actin occurs at the barbed end, leading to filament elongation. Elongation will continue whilst the rate of elongation is greater than the loss of ADP-actin from the pointed end. Profilin preferentially binds to ATP-actin, inhibits nucleation and accelerates filament elongation in vivo. Depolymerization: When the dissociation rate of ADP-actin exceeds the rate of ATP-actin association, the filament shrinks. In vivo, this is aided by cofilin, which can severe filaments into short fragments and promote subunit loss from the pointed ends. Actin treadmilling occurs when the rate of association of ATP-actin and the rate of loss of ADP-actin are balanced. Related links: Filament Polarity: http://www.mechanobio.info/topics/cytoskeleton-dynamics/go-0005856/go-0005884 Capping Protein: http://www.mechanobio.info/Home/glossary-of-terms/mechano-glossary--a/capping-protein Actin Nucleation: http://www.mechanobio.info/modules/go-0045010
|2||Spire mediated Actin Filament Nucleation |
Read more about actin nucleation: http://www.mechanobio.info/Home/topics/Mechanobiology/What-is-the-Role-of-Actin-Filaments-in-Mechanotransduction/actin-filament-treadmilling Source: Janet Iwasa
|3||Formin mediated actin nucleation and filament assembly |
Formins promote the elongation of preexisting filaments by removing barbed end capping proteins and forming a sleeve around the actin subunits. Formins are also capable of actin nucleation, a process which is spatiotemporally coupled with actin disassembly. Formins nucleate and polymerize actin filaments at focal adhesions at a rate of around 0.3 µm/min. Inhibiting formin protein expression results in a decreased filament elongation rate (0.1 µm/min), coupled with abnormal stress fiber morphology and an accumulation of actin binding proteins (e.g. α-actinin) Formins could, in theory, contribute to protrusive forces by remaining attached to the barbed end of actin filaments Read more at MBInfo: http://www.mechanobio.info/modules/go-0070649
|4||Muscle contraction |
muscle contraction video
|5||Piezo1 Ion Channel Gating Mechanism |
Proposed model of mechanical activation of a Piezo1 ion channel. Based on “Ge et al. 2015. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature, 527: 64-69”. Molecular structure derived from PDB (ID: 3JAC), with peripheral blades added by the artist.
|6||Focal adhesions grow in response to force |
Source: Yuliya Zilberman, Marine Biological Laboratory, USA (Summer course, 2005). Permission: Alexander Bershadsky, Mechanobiology Institute, Singapore. Upon removal of a myosin inhibitor, the cells start to contract. Force generated by myosin contractility enables punctate nascent adhesions to grow in size, as shown by the accumulation of GFP-paxillin. Subsequently they mature into focal adhesions. For further information on this research, visit http://mbi.nus.edu.sg/alexander-bershadsky/
|7||Focal adhesions form during lamellipodial protrusion and are essential for cell spreading |
Source: Leticia Carramusa, Weizmann Institute of Science, Israel Permission: Alexander Bershadsky, Mechanobiology Institute, Singapore Upon neuregulin treatment, cell-surface receptors Erb B3/B4 induce lamellipodia formation, most probably through activation of the Rac-WAVE-Arp2/3 pathway. During lamellipodial protrusion, numerous focal adhesions form along the cell periphery and can be visualized as fluorescent spots (GFP-VASP). For further information on this research, visit http://mbi.nus.edu.sg/alexander-bershadsky/
|8||Step Four of Cell Movement: Retraction |
Dr. Jim Bear provides a tutorial on the four steps of cell movement. This cell movie shows the fourth step in cell movement - retraction.
|9||Lateral waves of the lamellipodium |
Source: Giannone G et al. Cell (2007) 128:561-575. Permission: Prof Mike Sheetz, Mechanobiology Institute, Singapore and Columbia University, New York, USA. (http://www.columbia.edu/cu/biology/faculty/sheetz/) Differential interference contrast microscopy of mouse embryonic fibroblasts plated on fibronectin, 100x (22pix/μm), 0.33 s/frame.
|10||Filopodia dynamics |
Source: Hu Xian, Edna, Mechanobiology Institute, Singapore. CV-1 cells grown on glass coverslips were imaged live using API Delta Vision (100x) for 2min. The dynamic behavior of filopodia such as extension, lateral movement, fusion and retraction can be observed. For more information on this research topic, please visit Sheetz Lab: http://www.columbia.edu/cu/biology/faculty/sheetz/
|11||Sliding Filament |
sliding filament theory of muscle contraction - created by Sara Egner as part of UIC's biomedical visualization program **Some of you have noticed that there is a mispronunciation in this animation. It's true. ATP stands for adenosine triphosphate, and ADP for adenosine diphosphate. Please don't be confused on my account. ~Sara (anatomyandart.com/blog)