Research

The overarching goal of the CTELab is to investigate how cells and tissues become fragile in disease, and to reverse engineer the mechanical properties of cells and tissues for use in regenerative medicine.

Diseases of Tissue Fragility

Mechanical integrity and force transmission in even the simplest tissues is critical to their proper function. This is particularly apparent in diseased states where point mutations to cytoskeletal or junctional proteins result in tissue mechanical failure such as blistering, cracking and hemorrhaging.  Characterizing the mechanical properties of single cells and simple tissues from a materials science and engineering perspective could lead to a better understanding of diseases of cell and tissue fragility. The lab is currently interested in understanding the mechanical properties of tissues such as skin, and genetic diseases of skin tissue fragility.

Mechanisms of Traumatic Brain Injury

In collaboration with the Impact Mechanics Lab at Carleton University, we are investigating the role of cytoskeletal proteins expressed in cells in the central nervous system in traumatic brain injury. To investigate cellular responses to mechanical strain amplitude and strain rate, we have built our own mechanical testing setup for subjecting neurons and astrocytes to pathological loading conditions associated with Traumatic Brain Injury.

Cell, Cytoskeletal, and Polymer Mechanics

One of the major determinants of cell mechanical properties is a filament forming protein called actin. Actin filaments are assembled into distinct higher order structures (including bundles, meshes and cables) by an array of specialized binding and crosslinking proteins. The organization of actin filaments within each structure is directly linked to its function through the ability to generate specific mechanical forces. For example, aligned bundles of actin filaments in stress fibers pull on the extracellular matrix, and dendritic actin networks push the leading edge of migrating cells forwards. Missense mutations to actin crosslinking proteins are associated with a number of diseases including familial Focal Segmental Glomerulosclerosis (FSG), Periventricular nodular heterotopia (PVNH), Myofibrillar and Distal Myopathies, many of which present with symptoms associated with compromised cellular force generation and tissue fragility. Understanding how actin filaments are organized into distinct force generating structures through the activity of filament crosslinking proteins is therefore interesting and important from both a biophysical and clinical perspective. The lab takes a multidisciplinary approach to understanding how actin filaments are organized into force generating structures using tools such as machine learning for image analysis and purification of actin regulatory proteins to characterize their behavior in vitro.

Tool Development

The length scale of a single cell or simple tissue is on the order of tens to hundreds of micrometers. In order to study the mechanical properties of samples on this length scale, we can adapt and shrink down common tools for mechanical testing. Additional constraints on making these measurements are that the sample is alive and needs to be kept in conditions that are as close to physiologically relevant as possible. Engineering tools for studying biological systems presents an intriguing problem and often requires creative solutions. The lab uses established techniques such as Optical Microscopy and Atomic Force Microscopy but also develops new tools that provide quantitative measurements of the behavior of biological samples in a controlled environment, across a range of length scales.

Our lab has developed a home built Atomic Force Microscope that can be used to measure the mechanical properties of single cells and simple tissues (publication).