Research @ MBI
Understanding the molecular basis for mechanotransduction
In cells and tissues, the integration and propagation of mechanical signals is facilitated by the activity of molecular machines; small groups of proteins that detect and respond to mechanical stimuli by transferring physical forces to other cellular components, or facilitating their conversion to biochemical signals.
The information obtained during this process, which is known as mechanosensing, helps in cellular decision making.This is particularly important during development, when stem cells are differentiating to become specific cell types, and during wound healing or tissue repair.
At MBI, we are exploring mechano-transduction though four major research programs: molecular, cellular, tissue, and through technological innovations.
Cells can measure the stiffness of the surface on which they are growing and they can detect and respond to tension from neighboring cells within a tissue. Understanding how individual cells and proteins contribute to the mechanotransduction of physical force, is a major focus in the research conducted at the MBI. Dissecting the nanoscale architecture of various molecular machines involves the manipulation of specific cellular components, and at times, single proteins or specific protein domains. We can then monitor any subsequent effects.
Crucial to these efforts is the ability to control and modify the physical parameters of the cellular microenvironment. This means growing cells on substrates of a specific stiffness, pattern or shape. The effect of any molecular manipulation must then be monitored by quantifying the forces generated by cells or individual proteins, or visualizing the effects using super-resolution microscopy techniques.
Molecular Mechanisms of Mechanobiology
At MBI, we investigate how groups of proteins come together to form modular functional units that are capable of mediating diverse cellular functions by sensing and relaying mechanical signals between various components of the cell. More
Cell-Matrix / Cell-Cell Mechanotransduction
MBI is working to understand how a cell’s behavior within a tissue is guided by its communication with neighboring cells and the extracellular matrix through the formation of protein-based adhesion complexes. More
Mechanotransduction in Tissue Development
At the MBI, we apply biophysical principles to study the highly-coordinated orchestration of cellular events in a tissue, and understand its relevance during the development of an embryo as well as during tissue repair in adult organisms. More
Technology Innovation for Mechanobiology
The state-of-the-art technology at MBI has expanded our understanding of cell mechanics, enabling us to manipulate the physical properties of the cellular microenvironment as well as to precisely quantify cellular response to mechanical signals. More
Recent Featured Research
Bridging the (BP)GAP in metastasis
A collaborative study between researchers at MBI and scientists locally and overseas discovered how a scaffolding protein synchronizes, in space and time, two important regulatory proteins driving cell migration Learn more
The Crown JeWell of organoid imaging
An interdisciplinary team from MBI combined imaging, microfabrication, and biology to develop JeWells - an innovative platform for growing and imaging organoids in 3D. Learn more
Building a mechanobiological signaling scaffold for the heart
A collaboration between MBI scientists and clinical researchers revealed how a scaffolding protein integrates biochemical and mechanical signals to control cardiac muscle cell differentiation. Learn more
Featured Publication
The Michael Sheetz Lab
The Sheetz Lab is engaged in studies to understand the detailed molecular mechanisms involved in a variety of phenomena from cancer metastasis to brain function. Learn more.
The Hanry Yu Lab
The Yu Lab’s research spans from basic biological studies to integrative engineering of biomedical devices that facilitate the translation of systems-level understanding of biological functions into significant applications. Learn more.
The Cell as a Machine
Part of Cambridge Texts in Biomedical Engineering
Published through Cambridge University Press and available in March of 2018, MBI Principal Investigators Michael Sheetz and Hanry Yu have written a unique introductory text explaining cell functions using the engineering principles of robust devices.
Adopting a process-based approach to understanding cell and tissue biology, the book describes the molecular and mechanical features that enable the cell to be robust in operating its various components, and explores the ways in which molecular modules respond to environmental signals to execute complex functions.
Part I. Principle of Complex Function in Robust Machines:
- Robust self-replicating machines shaped by evolution
- Complex functions of robust machines with emergent properties
- Integrated complex functions with dynamic feedback
- Cells exhibit multiple states, each with different functions
- Life at low Reynolds number and the mesoscale leads to stochastic phenomena
Part II. Design and Operation of Complex Functions:
- Engineering lipid bilayers to provide fluid boundaries and mechanical controls
- Membrane trafficking – flow and barriers create asymmetries
- Signaling and cell volume control through ion transport and volume regulators
- Structuring a cell by cytoskeletal filaments
- Moving and maintaining functional assemblies with motors
- Microenvironment controls life, death and regeneration
- Adjusting cell shape and forces with dynamic filament networks
- DNA packaging for information retrieval and propagation
- Transcribing the right information and packaging for delivery
- Turning RNA into functional proteins and removing unwanted proteins
Part III. Coordination of Complex Functions:
- How to approach a coordinated function – cell rigidity sensing and force generation across length scale
- Integration of cellular functions for decision making
- Moving from omnipotency to stable differentiation
- Cancer versus regeneration – the wrong versus right response to the microenvironment.
MBI Video
Hew Choy Leong receives Alumni Award for Academic Achievement
Emeritus Professor Hew Choy Leong, Senior Advisor to MBI, is honoured with an Outstanding Alumni Award for Academic Achievement.
Prof Rong Li elected President of the American Society for Cell Biology for 2026
MBI Director Professor Rong Li, has been elected by members of the American Society for Cell Biology (ASCB) to serve as President of the Society in 2026. She will serve as President-Elect on the ASCB Executive Committee beginning 1 January 2025, before starting her term as President on 1 January 2026.
Hilary Lappin-Scott visiting from Cardiff
Prof. Hilary Lappin-Scottvisiting MBI on 27th November, 2019, for an afternoon of talks, discussion and networking opportunities.
MBI Publications
Latest Publications
- Sheng B, Pushpanathan K, Guan Z, Lim QH, Lim ZW, Yew SME, Goh JHL, Bee YM, Sabanayagam C, Sevdalis N, Lim CC, Lim CT, Shaw J, Jia W, Ekinci EI, Simó R, Lim L, Li H, and Tham Y. Artificial intelligence for diabetes care: current and future prospects. Lancet Diabetes Endocrinol 2024; 12(8):569-595. [PMID: 39054035]
- Zhu S, Loo YT, Veerapathiran S, Loo TYJ, Tran BN, Teh C, Zhong J, Matsudaira P, Saunders TE, and Wohland T. Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition. Biophys J 2024;. [PMID: 39049492]
- Lin K, Gujar MR, Lin J, Ding WY, Huang J, Gao Y, Tan YS, Teng X, Christine LSL, Kanchanawong P, Toyama Y, and Wang H. Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling. Sci Adv 2024; 10(30):eadl4694. [PMID: 39047090]
- Zhang Y, Du J, Liu X, Shang F, Deng Y, Ye J, Wang Y, Yan J, Chen H, Yu M, and Le S. Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification. Nat Commun 2024; 15(1):6151. [PMID: 39034324]
- Johnson BA, Liu AZ, Bi T, Dong Y, Li T, Zhou D, Narkar A, Wu Y, Sun SX, Larman TC, Zhu J, and Li R. Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids. Mol Biol Cell 2024;:mbcE24040166. [PMID: 38985518]
- Morales-Camilo N, Liu J, Ramírez MJ, Canales-Salgado P, Alegría JJ, Liu X, Ong HT, Barrera NP, Fierro A, Toyama Y, Goult BT, Wang Y, Meng Y, Nishimura R, Fong-Ngern K, Low CSL, Kanchanawong P, Yan J, Ravasio A, and Bertocchi C. Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction. Nat Commun 2024; 15(1):5608. [PMID: 38969637]
- Chua XL, Tong CS, Su M, Xǔ XJ, Xiao S, Wu X, and Wu M. Competition and synergy of Arp2/3 and formins in nucleating actin waves. Cell Rep 2024; 43(7):114423. [PMID: 38968072]
- Ma Y, Li Z, Luo Y, Chen Y, Ma L, Liu X, Xiao J, Huang M, Li Y, Jiang H, Wang M, Wang X, Li J, Kong J, Shi P, Yu H, Jiang X, and Guo Q. Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment. ACS Nano 2024;. [PMID: 38946122]
- Lin S, Prost J, and Rupprecht J. Curvature-induced clustering of cell adhesion proteins. Phys Rev E 2024; 109(5-1):054406. [PMID: 38907394]
- Zhang X, Ruan L, Wang H, Zhu J, Li T, Sun G, Dong Y, Wang Y, Berreby G, Shay A, Chen R, Ramachandran S, Dawson VL, Dawson TM, and Li R. Enhancing mitochondrial proteolysis alleviates alpha-synuclein-mediated cellular toxicity. NPJ Parkinsons Dis 2024; 10(1):120. [PMID: 38906862]
Bridging the (BP)GAP in metastasis
A collaborative study between researchers at MBI and scientists locally and overseas discovered how a scaffolding protein synchronizes, in space and time, two important regulatory proteins driving cell migration Learn more
The Crown JeWell of organoid imaging
An interdisciplinary team from MBI combined imaging, microfabrication, and biology to develop JeWells - an innovative platform for growing and imaging organoids in 3D. Learn more
Building a mechanobiological signaling scaffold for the heart
A collaboration between MBI scientists and clinical researchers revealed how a scaffolding protein integrates biochemical and mechanical signals to control cardiac muscle cell differentiation. Learn more
