A method to study cardiovascular disease is developed by Virginia Tech aand the University of Pittsburghh School of Medicine.
Cardiovascular disease is the number one cause of death in the United States. When the largest artery in the body, known as the aorta is affected by the disease, it can split or dilate, resulting in an aneurysm that can be fatal.
The schools developed a method to look at the role of biomechanical forces and their disruption in diseased pathologies using relevant platforms that provide a window to study disease manifestation and progression. This platform, called nanonet force microscopy or NFM, is the first of its kind to measure single cell fiber forces, both under passive conditions and in the presence of disease conditions.
Amrinder Nain, associate professor of mechanical engineering in the College of Engineering at Virginia Tech, pioneered NFM to use extracellular mimicking fibers in a controlled and repeatable manner. Together, with Julie Phillippi, an assistant professor in the Department of Cardiothoracic Surgery at the University of Pittsburgh, they question what the cells experience in the body by measuring individual cellular force.
Smooth muscle cells present in the walls of blood vessels undergo expansion and contraction. The force signatures that come from this involve the interplay between the innate contractility of the cells and the forces exerted on that cell by fibrous extracellular matrix, which structurally and functionally support these cells.
“Everything in nature exerts and experiences a physical force,” said Nain. “This platform measures both simultaneously.”
Phillippi looks at the matrix and cell forces in blood vessel smooth muscle cells as a window to understand aortic disease.
“The key idea behind our study is to show that disease mechanisms might be detectable at the single cell level,” Phillippi said.
Nain and Phillippi used cells from healthy people in the study. In the future, they want to take advantage of the large supply of patient samples from healthy and diseased people established by Thomas Gleason, chief of the Division of Cardiac Surgery at the University of Pittsburg, to determine force signatures for different type of cells in blood vessels under various conditions.
The technique has much broader applications as it represents a new method of disease modeling that could be built into drug testing platforms in the future. In a broader context, Nain thinks the ability to achieve precise control on fiber diameter, spacing and orientation to mimic native fibrous environments, will allow NFM to interrogate the push nd pulls in a cell’s journey in developmental, disease and repair biology.
The expanded research team is composed of two undergraduate students, Christopher Delaughter of Mount Jackson, Va., and Matthew Apperson of Norfolk, Va., graduate student Alexander Hall of Gastonia, N.C., and Kevin Sheets, former doctoral student, all of the Virginia Tech Department of Mechanical Engineering. The team also includes Patrick Chan, a clinical resident of the University of Pittsburgh.