Decoding the Living Machine

Research2019-07-22T09:40:06+08:00

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

Featured Publication

sheetzThe 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.

sheetzThe 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.

Read more at Cambridge University Press

Featured Video

photos-portraits-square-kenneyThe Linda J Kenney Lab

Kenney’s laboratory is interested in signal transduction and the regulation of gene expression in prokaryotes. They are studying the two-component regulatory system EnvZ/OmpR that regulates the expression of outer membrane proteins as well as many other genes. Their present work focuses on how OmpR activates genes required for systemic infection in Salmonella enterica. Learn more.

Salmonella Lifestyle Choices

A bacterial molecular switch for infection or dormancy

Professor Linda Kenney describes a recent project from her lab on Salmonella pathogenesis. In this study, MBI Senior Research Fellow Dr Stuti Desai and colleagues discovered that the bacterial protein SsrB is the molecular switch for determining whether Salmonella infections become acute and virulent, or remain in a dormant carrier state.

Researchers from the Mechanobiology Institute (MBI), National University of Singapore have discovered that the bacterial protein SsrB is the molecular switch for determining whether Salmonella infections become acute and virulent, or remain in a dormant carrier state. This paper was published in eLife (Desai et al., The horizontally-acquired response regulator SsrB drives a Salmonella lifestyle switch by relieving biofilm silencing, February 2, 2016, eLife 2016; 5: e10747, doi: 10.7554/eLife.10747).

Read the article on MBInsights