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MBI PhD Oral Defense

Time: 2.30pm
Date: Tuesday, 26 November 2019
Venue: T-Lab, Level 5 Meeting Room 1

Supervisors: Prof. Virgile Viasnoff and Prof. Alexander Bershadsky

Interrelationship Between Contractility And Dynamics Of Actomyosin System In Non-Muscle Cells

by SHI Shidong, Viasnoff’s Group

Contractile actomyosin stress fiber (SF) systems in non-muscle cells are essential for a variety of cellular processes including adhesion and morphogenesis. While transmitting long-sustained non-muscle myosin II (NM II)-generated force to the substrate through focal adhesions (FAs), ventral stress fiber (VSF) is surprisingly a highly dynamic system subjected to constant polymerization and depolymerization. However, how actin dynamics (in particular, polymerization-depolymerization driven flow along the fibers) and NM II dependent contractility are related to each other in matured VSFs still remains elusive. To this end, I manipulated either actin polymerization or forces in VSFs to investigate how they influence one another. Surprisingly, pharmacological inhibitors SMIFH2 (an inhibitor of formin-family proteins) strongly inhibited the forces exerted by VSFs onto the substrates. I hence proposed that besides working as actin elongation factors, formins could physically link actin filaments with each other, thus participating in both actin polymerization and force transmission processes. On the other hand, drug inhibition of NM II generated forces prevented actin polymerization along VSFs. Furthermore, cyclic stretching rescued the actin polymerization in cells with inhibited formins, but not in cells with inhibited NM II. Therefore, I hypothesized that NM II generated force may feedback to mechano-sensitive formins to regulate actin polymerization while the counter forces generated by NM II filaments are essential for the force transmission along VSFs.       Our results revealed that VSFs are dynamic viscoelastic systems, in which NM II driven contractility and actin dynamics are fine-tuned with each other.

 

**Please note the examination following the seminar is closed-door**

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About NUSA leading global university centred in Asia, NUS is Singapore's flagship university, offering a global approach to education and research with a focus on Asian perspectives and expertise.

About the Mechanobiology Institute, National University of Singapore

About MBIOne of four Research Centres of Excellence at NUS, MBI is working to identify, measure and describe how the forces for motility and morphogenesis are expressed at the molecular, cellular and tissue level.
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