We all know the power of touch: A whack on the skull – or a hug – can convey more information than other forms of communication ever can. It turns out the same is true inside our bodies, where just the right touch among blood cells can mean the difference between good health and chronic conditions like heart disease and diabetes.
The power of touch among blood cells is the focus of a team of biomedical engineers at the University of Rochester that has received an $11.5 million grant from the National Institutes of Health. The five-year program takes aim at a process that is fundamental to our health: How do mechanical forces govern our white blood cells and assure that they protect our bodies from invaders like the flu? What forces help keep those cells from getting out of control and attacking our own tissues?
The group is focusing on white blood cells known as neutrophils, which are the body’s first responders to inflammation and infection, and how those cells interact with the blood vessel lining known as the endothelium. The cells float along in the bloodstream and make the round trip through the human body in about one minute, always on patrol, looking for invaders. When they see an intruder, they call in reinforcements, pursue and destroy – but only in partnership with the blood vessel lining, which gives the cells access to tissue, like a police officer who clears the way for other officers to pursue the target. The physical touching between the cells and the lining is crucial.
“This is your first line of defense against disease,” says Richard Waugh, Ph.D., chair of the Department of Biomedical Engineering and leader of the team of engineers and scientists who received the grant. “Some of the biggest health problems that people face result from inappropriate responses of white blood cells. Understanding the details of our defenses, at the level of the blood cell, is crucial for developing new treatments and for controlling inappropriate immune responses.”
The forces at work are daunting, partly because each cell has a complex surface topography, with dozens of small molecular projections that give it a ruffled appearance, kind of like a tiny raisin. Those projections serve as signals that help determine where white blood cells will exit the bloodstream and fight infections.
Imagine blood vessels and cells coated with patches of Velcro – actually “adhesion molecules” – whose stickiness can be activated or deactivated. Signals from moment to moment turn on or off the Velcro from place to place, determining exactly when and where cells stick and accumulate. When some adhesion molecules are activated, cells begin to roll slowly along a blood vessel wall; when others turn on, the cells are snagged by the blood vessel wall and ultimately allowed admittance to our tissues, where they fight disease. The Rochester team has shown how physical forces and patterns of blood flow are crucial to the process.
When the sticking process goes awry, disease occurs. Painful and harmful inflammation occurs when white cells are extremely active. Autoimmune diseases like diabetes, multiple sclerosis and lupus happen when our white blood cells attack our own tissues – somehow our cells have gained admittance and are allowed to congregate and operate where they shouldn’t. The same is true of much heart disease, where atherosclerosis occurs when white blood cells cause blockages by narrowing blood vessels.
Understanding how forces affect white blood cells offers a new way to fight many of these diseases. Doctors might be able to funnel cells directly where they’re needed, allowing them to boost the body’s immune response without causing side effects. Engineers are already working on devices that could filter out harmful cells by making them stick, and devices that capture rare but crucial cells such as stem cells and then release them as needed.
The team brings a unique engineering viewpoint to a domain – the human body – that is often governed by physicians. The engineers are building artificial systems to simulate the subtle forces on blood cells; they’re developing computer models that simulate how blood cells get buffeted about by other cells in the circulation; and they use the tiniest of tools to measure how cell-like beads stick to surfaces.
“Many people with an expertise in fluid mechanics might go into the petroleum industry, or public works, or the food industry. Here we’re using the same expertise to get a unique look into one of the most basic processes in our bodies,” says Waugh. “This type of work takes a special breed of engineer willing to deal with messy systems, as most biological systems tend to be.”
The grant will fund projects headed by five scientists. In addition to Waugh, leading projects at Rochester are Ingrid Sarelius, Ph.D., Michael King, Ph.D., and Philip Knauf, Ph.D., all of the University; and Daniel Hammer, Ph.D., of the University of Pennsylvania.
Since its birth in 2000, Biomedical Engineering has become the fastest-growing department at the University, with 12 faculty members, thanks largely to significant funding from the Whitaker Foundation. Nearly 150 undergraduate students have majored in biomedical engineering in the past five years. This weekend the University broke ground on a new $30 million building to house the Department of Biomedical Engineering as well as office and laboratories for the Institute of Optics.