Integrated Mechanobiology Research

Integrated Research Thrusts (IRTs)

IRTs focus our research on how plant and animal cells integrate mechanical cues from their microenvironment into biochemical and genomic pathways that drive cell, tissue, and organ function over multiple length and time scales.

The IRTs represent collaborative efforts of preeminent laboratories and focus on:

  • Cell-Matrix Dialogue
  • The Nucleus and Mechanical Memory
  • Tissue Mechanics in 4D

IRT 1: Cell-Matrix Dialogue

Uncovering and engineering the recursive dialogue between cells and their extracellular environment

Goal: To uncover fundamental mechanisms underlying the recursive dialogue between plant and animal cells and their cell walls or extracellular matrix (ECM). We harness this understanding to engineer the responses of plants and animals to mechanical cues generated by environmental stresses, injury, and fibrosis.

Fundamental questions include:

  • How do cells respond to mechanical stimuli that vary in length and time scales?
  • How do cells discriminate between mechanical information in their local environment and integrate information with internal and external biochemical signals?
  • Can we engineer cells and their ECM/cell walls to create desired functional outputs?

IRT 2: The Nucleus and Mechanical Memory

Designing mechanically responsive memories in DNA

Goal: To develop foundational knowledge to enable the rational design of mechanically responsive chromatin and genetic programs. With this knowledge, new technologies will be developed that can strip unwanted mechanical memories or impart new artificial ones to enable more efficacious and economically feasible cell-based therapies.

Fundamental questions include:

  • How does the spatial redistribution of epigenetic modifiers, nuclear-cytoskeletal factors, and mechanosensitive proteins within the cell enable mechanical memory?
  • How do temporal variations in the kinetics of epigenetic modifications, mechanosensitive gene expression, and protein production alter the rates of memory acquisition and degradation?
  • How do mechanical changes in nuclear structure and function, chromatin organization, and cytoskeletal remodeling alter the potential for mechanical memory and developmental output?

IRT 3: Tissue Mechanics in 4D

Pioneering the assembly of plant and animal cells into tissue-like structures and new technologies

Goal: To pioneer methods to assemble plant and animals cells into tissue-like structures and to use these platforms to gain insights into the mechanobiology of these tissues and the cells within them. These new technologies will include new synthetic materials that mimic specific extracellular matrices, fabrication and microfluidic approaches to generate biomimetic cultures that capture the structural complexity of native tissues, and new theoretical and computational approaches to model complex structures.

Fundamental questions include:

  • How do cells distinguish and respond to different types of mechanical stimuli?
  • How does the organization of cells enhance or dampen responses to mechanical forces?
  • How do cells integrate mechanical and biochemical signals to generate a coherent response?
  • How do cells responding to mechanical perturbations coordinate with neighboring cells to generate coordinated tissue-level responses?
  • Can we engineer cells or structures to dampen, amplify, or fundamentally alter how cells sense and respond to forces?