Michael SHEETZ
Founding Director and Collaborator, Mechanobiology Institute, National University of Singapore
Affiliations
Professor, Department of Biochemistry & Molecular Biology, UTMB Health
How does nucleation of actin initiate lamellipodia formation?
How does nucleation of actin initiate lamellipodia formation? In the first phase of lamellipodia formation, actin filament polymerization produces a protrusive force on the cell membrane that promotes the spreading out and enlargement of [...]
What mechanisms drive extension, pause and stasis of the lamellipodia?
What mechanisms drive extension, pause and stasis of the lamellipodia? Extension of the newly formed actin filament branches occurs at the interface between the leading edge and the existing actin filament network [1] and [...]
How do focal adhesions act as molecular clutches in lamellipodia?
How do focal adhesions act as molecular clutches in lamellipodia? Once formed, focal adhesions essentially act as “molecular clutches”, promoting protrusion at the leading edge whilst suppressing membrane contraction (reviewed in [1] [2][3]). Adhesions [...]
What mechanisms drive retraction of the trailing edge?
What mechanisms drive retraction of the trailing edge? Protrusion at the front and retraction at the rear are key force-generating processes at the cell periphery that culminate in the translocation of the cell. For [...]
What are invadopodia?
What are invadopodia? Invadopodia are actin-rich structures that are present at the basal surfaces of cells that are capable of crossing extracellular barriers, such as cancer cells. The primary function of invadopodia appears to [...]
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
Dr Hu Xian Edna visiting from University of Oslo
Dr Hu Xian Edna from University of Oslo is visiting from 25 Mar - 23 Apr 2019.
Prof GV Shivashankar featured on Becoming Human, Channel News Asia
MBI Principal Investigator and Deputy Director Professor GV Shivashankar is featured in the Channel News Asia documentary series, Becoming Human: Unnatural Genius to discuss how his lab uses AI and and nuclear mechanogenomic architecture to detect early stage cancer cells.
Myosin motors show their muscle
How cells generate high forces for testing the softness of their environment
Chloe May Simpson
Alumni, Sheetz Lab
Aaron Joseph Farrugia
Senior Research Fellow, Bershadsky Lab
Geetika Sahni
Senior Research Fellow, Viasnoff Group
The guiding hands (and feet)
Focal adhesions in embryonic stem cells
MBI Senior Research Fellow Rishita Changede wins Best Presentation at TOPIM
MBI Senior Research Fellow Rishita Changede wins the Best Presentation award at the TOPIM Winter Conference 2019, for her presentation on the role of integrin nanoclusters as the basis for the formation of cell-matrix adhesions that aid in sensing the mechanical properties, such as rigidity, of the underlying tissue.
Ratna Prasuna Vogirala
Alumni, Shivashankar Group
Mechanics shaping the germline
Actomyosin corsets protect the epithelium
Moving with the flow
Environmental sensing through intracellular dynamics determines how cells migrate
MBI welcomes students from Seoul National University
SNU students toured the MBI labs, familiarizing themselves with the methodology and applications of state-of-the art techniques like microfabrication, micropatterning, and superresolution microscopy through demonstrations conducted by MBI researchers.
