Michael SHEETZ
Founding Director and Collaborator, Mechanobiology Institute, National University of Singapore
Affiliations
Professor, Department of Biochemistry & Molecular Biology, UTMB Health
YAN Chengrui
PhD Student, Class of August 2025, Yan Jie Group
NGUYEN Dinh Thach Lam
PhD Student, Class of August 2025, Hirashima Group
Miguel SOON Jun Yi
PhD Student, Class of August 2025, Low Group
LYU Min
PhD Student, Class of August 2025, Lim Group
HOANG Mai Thanh Truc
PhD Student, Class of August 2025, Yu Group
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
What are Contractile Fibers?
What are Contractile Fibers? Certain myosin isoforms (i.e. myosin II) form bipolar assemblies via the extended coiled-coil domains in the heavy chains (see also “thick filaments”). Actin “thin filaments” with opposite polarity associate with [...]
What are Blebs?
What are Blebs? Blebs are blister-like protrusions that occur at the cell surface (reviewed in [1]). Blebs form, and function, in a series of defined steps. They typically grow to a length of around [...]
How is actomoysin contractility regulated?
How does the contractome protein network regulate actomyosin contractility? Non-muscle myosin II isoforms have a similar structure and function to their muscle equivalents. However, their interaction with actin serves to generate cellular forces rather [...]
What is Actomyosin?
What is Actomyosin? Actomyosin refers to the actin-myosin complex that forms within the cytoskeleton. Actomyosin is inherently contractile, with the myosin motor protein able to pull on actin filaments. This property gives rise to [...]
What are lamellipodia and lamella?
What are lamellipodia and lamella? The lamellipodia and lamella are plate-like extensions of the cell that play crucial roles in both cell motility and migration, and mechanosensing. These structures form and function over distinct [...]
How do blebs expand and retract?
How do blebs expand? Expansion lasts between 5 to 30 seconds, following bleb initiation and preceding reformation of the cortical actomyosin cytoskeleton just beneath the membrane [1]. During this time, the bleb proceeds to [...]
What are filopodia?
What are filopodia? Filopodia (singular filopodium) are thin membrane protrusions that act as antennae for a cell to probe the surrounding environment [1][2][3]. Nonprotruding filopodia are mechanistically related to microspikes [4]. Filopodia are commonly [...]
What is the first step in filopodium formation?
What is the first step in filopodium formation? Actin nucleation initiates filopodium formation The first step in the formation of a filopodium is the nucleation of actin filaments from G-actin monomers. This is facilitated [...]
How does cross-linking of actin filaments aid in filopodia extension?
How does cross-linking of actin filaments aid in filopodia extension? Once nucleation has taken place, actin filaments begin to extend. This process is primarily facilitated by members of the formin family of proteins, however [...]
How do filopodia pull on a substrate?
How do filopodia pull on a substrate? Although a reterograde motion of actin filaments is intrinsic in the formation of filopodia, the forces generated by actin treadmilling are too weak to facilitate the “pulling” [...]
How do filopodia move dynamically?
What causes filopodia retraction and collapse? Binding of filopodia to certain ligands or substratum may hinder filament assembly, thereby leading to changes that promote retraction, collapse or growth cone turning [1][2]. For example, substrate [...]
How do filopodia attach to the surrounding substrate?
How do filopodia attach to the surrounding substrate? A diverse array of cellular responses can result when a filopodium makes contact with a ligand or substrate. These responses are dependent on the coupling of [...]
