Cell Migration in Disease Group

All cells in our body have the ability to move, a critical feature in many health and disease situations. However, cell motility is rarely random. Most often, cells can follow directional cues in the form of chemical stimuli (aka chemotaxis). For example, white blood cells (leukocytes) are able to follow gradients of signaling molecules diffusing from sites of acute or chronic inflammation. Less often, cells can move along heterogeneous structures in tissues (aka mechanotaxis). For example, cancer cells can spread away from the primary tumor by following the trajectories of lymphatic vessels, nerves, white matter tracts. Understanding how the cells could accomplish such complex tasks might reveal new ways to control cell motility for therapeutic purposes in inflammatory and degenerative diseases or cancer. To gain useful insights into the mechanisms of cell motility, we started by designing new tools to allow us to measure the directionality and speed characteristics of moving cells. We can now do this with unprecedented precision and we made several unexpected observations. We defined for the first time a set of “normal values” for directional decisions and speed in neutrophils from healthy people. We measured how neutrophil speed is temporarily decreased after burn injuries, favoring infections. We showed that cancer cells can be persistently guided over hundreds of microns in one direction along microscale structures. Ultimately, all these new findings will converge towards new therapeutic strategies for modulating the motility of various cells, in a broad range of conditions that span from acute sepsis to chronic inflammation and from cancer invasion to tissue regeneration.

Examples of ongoing projects include:

• Microfluidic platform to study modulation of microglia migration by amyloid-beta
• Microfluidic assays to quantify neutrophil motility in burn patients
• Cancer cell migration in confined microfabricated environments
• Neutrophil decision making in response to spatial and temporal gradients

Representative Publications:

• Irimia D. Microfluidic Technologies for Temporal Perturbations of Chemotaxis. Annual Review of Biomedical Engineering 2010; 12: 259-284.
• Ambravaneswaran V, Wong IY, Aranyosi AJ, Toner M, Irimia D.  Directional Decisions during Neutrophil Chemotaxis inside Bifurcating Channels. Integrative Biology 2010; 2(11): 639 - 647.
• Butler KL, Ambravaneswaran V, Agrawal N, Bilodeau M, Toner M, Tompkins RG, Fagan S, Irimia D. Burn Injury Inhibits Neutrophil Chemotaxis in Microfluidic Devices. PLOS One 2010; 5(7):e11921.
• Irimia D, Toner M. Spontaneous migration of cancer cells under conditions of mechanical confinement. Integrative Biology 2009; 1: 506-512.
• Irimia D, Liu SY, Tharp WG, Samadani A, Toner M, Poznansky MC. Microfluidic System for Measuring Neutrophil Migratory Responses to Fast Switches of Chemical Gradients. Lab on a Chip 2006; 6: 191–198.