Michael SHEETZ
Founding Director and Collaborator, Mechanobiology Institute, National University of Singapore
Affiliations
Professor, Department of Biochemistry & Molecular Biology, UTMB Health
Seeking Research Assistant in Transmission Electron Microscopy at the Mechanobiology Institute, NUS
We are seeking a Research Assistant in Transmission Electron Microscopy (TEM) at the Mechanobiology Institute, NUS
Seeking Research Fellow in Transmission Electron Microscopy at the Mechanobiology Institute, NUS
We are seeking a Research Fellow in Transmission Electron Microscopy at the Mechanobiology Institute, NUS
Hu Yuqi
Research Assistant, Yu Group
The Nano-Heartbuilder: BNIP-2 Influences Mechanosensing in Cardiomyoblast Differentiation
Researchers from the Low Lab at MBI discover a crucial role for the scaffold protein BNIP-2 in orchestrating focal adhesion dynamics during early heart development, offering new insights into heart regeneration strategies.
Shedding Light on Local Microtubule Regulation of Focal Adhesions
Researchers from the Bershadsky Lab at MBI utilized optogenetics to unlock the role of microtubules in regulating focal adhesion disassembly, an important step in cell migration. http://www.mbi.nus.edu.sg/featured-research/microtubules-and-cell-movement-a-closer-look-at-focal-adhesion-disassembly
Michael Sheetz
Collaborator
Research Areas
Cell migration, cell-cell and cell-substrate interaction
Research Interests
The morphology of cells, organs and whole organisms is determined by the generation of forces on the immediate environment, which is either extracellular matrix or adjacent cells. We are currently engaged in studies to understand the detailed molecular mechanisms involved in a variety of phenomena from cancer metastasis to brain function. Further, we are developing several new tools and protocols for measuring cell forces at the molecular level, which are revealing many new aspects of how cells can both generate and respond to external forces. We have an effort underway to define quantitatively the steps involved in cell adhesion to and spreading on a matrix-coated surface. Using a variety of cell lines that are missing proteins in various motility pathways, we are determining the quantitative changes in the spreading process. This will enable us to generate a detailed model of the process of spreading that will be a model for further studies of how cells differentiate, regenerate tissues or metastasize.
Biography
Hailing from Columbia University, Prof Michael Sheetz has more than 40 years’ experience in the biomedical field. Introduced to Singapore by Prof Hew Choy Leong of the National University of Singapore’s Department of Biological Sciences, Prof Sheetz was sought to lead an RCE project. This resulted in a two-year effort to organise and submit a proposal on Mechanobiology where Prof Sheetz set the theme and direction of the Mechanobiology Institute (MBI). As Founding Director of the MBI, he led the institute for 10 years and built it into a world-leading research centre in the field of mechanobiology.
Education
PhD California Institute of Technology
Recent Publications
- Jain K, Kishan K, Minhaj RF, Kanchanawong P, Sheetz MP, and Changede R. Immobile Integrin Signaling Transit and Relay Nodes Organize Mechanosignaling through Force-Dependent Phosphorylation in Focal Adhesions. ACS Nano 2025;. [PMID: 39760672]
- Lin S, Changede R, Farrugia AJ, Bershadsky AD, Sheetz MP, Prost J, and Rupprecht J. Membrane Tilt Drives Phase Separation of Adhesion Receptors. Phys Rev Lett 2024; 132(18):188402. [PMID: 38759206]
- Jain K, Minhaj RF, Kanchanawong P, Sheetz MP, and Changede R. Nano-clusters of ligand-activated integrins organize immobile, signalling active, nano-clusters of phosphorylated FAK required for mechanosignaling in focal adhesions. bioRxiv 2024;. [PMID: 38464288]
- Jain K, Pandey A, Wang H, Chung T, Nemati A, Kanchanawong P, Sheetz MP, Cai H, and Changede R. TiO2 Nano-Biopatterning Reveals Optimal Ligand Presentation for Cell-Matrix Adhesion Formation. Adv Mater 2024;:e2309284. [PMID: 38340044]
- Jain K, Lim KYE, Sheetz MP, Kanchanawong P, and Changede R. Intrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction. bioRxiv 2023;. [PMID: 38045378]
- Oh D, Liu X, Sheetz MP, and Kenney LJ. Small, Dynamic Clusters of Tir-Intimin Seed Actin Polymerization. Small 2023;:e2302580. [PMID: 37649226]
- Qin R, Melamed S, Yang B, Saxena M, Sheetz MP, and Wolfenson H. Tumor Suppressor DAPK1 Catalyzes Adhesion Assembly on Rigid but Anoikis on Soft Matrices. Front Cell Dev Biol 2022; 10:959521. [PMID: 35927990]
- Jain K, Kanchanawong P, Sheetz MP, Zhou X, Cai H, and Changede R. Ligand functionalization of titanium nanopattern enables the analysis of cell-ligand interactions by super-resolution microscopy. Nat Protoc 2022;. [PMID: 35896742]
- Toh PJY, Lai JKH, Hermann A, Destaing O, Sheetz MP, Sudol M, and Saunders TE. Optogenetic control of YAP cellular localisation and function. EMBO Rep 2022;:e54401. [PMID: 35876586]
- Oh D, Chen Z, Biswas KH, Bai F, Ong HT, Sheetz MP, and Groves JT. Competition for shared downstream signaling molecules establishes indirect negative feedback between EGFR and EphA2. Biophys J 2022;. [PMID: 35430415]
Lab Members
How do actin filaments depolymerize?
How do actin filaments depolymerize? Introduction to Actin Filament Depolymerization Whole cell motility and mechanosensing rely on the continual restructuring of the cytoskeleton, particularly within lamellipodia and filopodia; two dynamic structures that contribute to [...]
How does Arp2/3-mediate the nucleation of branched filaments?
How does Arp2/3-mediate the nucleation of branched filaments? The Arp2/3 complex is composed of 7 evolutionarily conserved subunits (Arp2, Arp3, ARPC1-C5) that are structurally similar to the barbed end of actin [1]. The complex [...]
How are actin filaments distributed in cells and tissues?
How are actin filaments distributed in cells and tissues? Actin filaments are widely distributed throughout cells, forming a range of cytoskeletal structures and contributing to an even broader range of processes. Some of the [...]
How do actin filaments grow?
How do actin filaments grow? Actin Filaments (F-actin) grow from the polymerization of G-actin monomers Actin is a highly abundant (10-100 micromolar on average),~42 kDa structural protein found in all eukaryotic cells (except for [...]
What is actin nucleation?
What is actin nucleation? The first step in actin polymerization is known as ‘nucleation’. This step sees the formation of an actin nucleus, which is essentially a complex of three actin monomers, from which [...]
Actin Crosslinking
Actin Crosslinking Crosslinking of actin filaments is a critical step in cell motility and is a fundamental process in filopodia protrusion and lamellipodia formation. Smaller cross-linking proteins that are more globular (e.g. fascin) [...]
What is the role of cortactin in actin polymerization?
What is the role of cortactin in actin polymerization? Cortactin is a class II nucleation promoting factor (NPF) that binds to actin filaments and influences their stability. Cortactin specifically stabilizes Arp2/3-mediated branch points along [...]
What is the role of formin in actin polymerization?
What is the role of formin in actin polymerization? Formins promote the elongation of pre-existing filaments by removing barbed end capping proteins and forming a sleeve around the actin subunits. Formins are also capable [...]
What is the steady state phase of actin polymerization?
What is the steady state phase of actin polymerization? In the steady state phase, the filament dynamics enter a state of equilibrium where monomer disassembly from the (-) end and polymerization at the (+) [...]
What factors regulate actin filament polymerization?
What factors regulate actin filament polymerization? Nucleation Promoting Factors (NPFs) (e.g. WASP, Scar/WAVE) modulate actin filament nucleation by bringing together actin monomers and pre-existing actin filaments, for example, during filopodial initiation where they recruit [...]
What factors influence actin filament length and treadmilling?
What factors influence actin filament length and treadmilling? Several factors influence actin filament length and treadmilling. ATP binding on G-actin and free ATP-G-actin concentration ATP-binding on actin subunits modulates the dynamics of filament assembly, [...]
I-BAR and Other Proteins/Factors
I-BAR and Other Proteins/Factors Proteins containing I-BAR (inverted Bin/amphiphysin/Rvs i.e. IRSp53 Missing-in-metastasis homology Domain or IMD) cooperate with various components of actin filament assembly, to promote filopodia protrusion, via several mechanisms including the stimulation [...]
