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Nanobiomechanics

Measuring the tiny forces acting on cells, Subra Suresh believes, could produce fresh understanding of diseases.

Most people don’t think of the human body as a machine, but Subra Suresh does. A materials scientist at MIT, Suresh measures the minute mechanical forces acting on our cells.

Medical researchers have long known that diseases can cause – or be caused by – physical changes in individual cells. For instance, invading parasites can distort or degrade blood cells, and heart failure can occur as muscle cells lose their ability to contract in the wake of a heart attack. Knowing the effect of forces as small as a piconewton – a trillionth of a newton – on a cell gives researchers a much finer view of the ways in which diseased cells differ from healthy ones.

Optical tweezers stretch a healthy red blood cell (top row), increasing the applied force slowly, by a matter of piconewtons. A cell in a late stage of malarial infection is stretched in a similar fashion (bottom row). The experiment illustrates how the infected cell becomes rigid, which prevents it from traveling easily through blood capillaries and helps cause the symptoms of malaria.
SUBRA SURESH

Nanobiomechanics

  • Key players

    Eduard Arzt – Structure and mobility of pancreatic cancer cells Max Planck at Institute, Stuttgart, Germany; Peter David and Genevieve Milon – Parasite-host interaction; mechanics of the spleen at Pasteur Institute, Paris, France; Ju Li – Models of internal cellular structures at Ohio State University; C. T. Lim and Kevin Tan – Red-blood-cell mechanics at National University of Singapore

Suresh spent much of his career making nanoscale measurements of materials such as the thin films used in microelectronic components. But since 2003, Suresh’s laboratory has spent more and more time applying nanomeasurement techniques to living cells. He’s now among a pioneering group of materials scientists who work closely with microbiologists and medical researchers to learn more about how our cells react to tiny forces and how their physical form is affected by disease. “We bring to the table expertise in measuring the strength of materials at the smallest of scales,” says Suresh.

One of Suresh’s recent studies measured mechanical differences between healthy red blood cells and cells infected with malaria parasites. Suresh and his collaborators knew that infected blood cells become more rigid, losing the ability to reduce their width from eight micrometers down to two or three micrometers, which they need to do to slip through capillaries. Rigid cells, on the other hand, can clog capillaries and cause cerebral hemorrhages. Though others had tried to determine exactly how rigid malarial cells become, Suresh’s instruments were able to bring greater accuracy to the measurements. Using optical tweezers, which employ intensely focused laser light to exert a tiny force on objects attached to cells, Suresh and his collaborators showed that red blood cells infected with malaria become 10 times stiffer than healthy cells – three to four times stiffer than was previously estimated.

Eduard Arzt, director of materials research at the Max Planck Institute in Stuttgart, Germany, says that Suresh’s work is important because cell flexibility is a vital characteristic not only of malarial cells but also of metastasizing cancer cells. “Many of the mechanical concepts we’ve been using for a long time, like strength and elasticity, are also very important in biology,” says Arzt.

Arzt and Suresh both caution that it’s too early to say that understanding the mechanics of human cells will lead to more effective treatments. But what excites them and others in the field is the ability to measure the properties of cells with unprecedented precision. That excitement seems to be spreading: in October, Suresh helped inaugurate the Global Enterprise for Micro-Mechanics and Molecular Medicine, an international consortium that will use nanomeasurement tools to tackle major health problems, including malaria, sickle-cell anemia, cancer of the liver and pancreas, and cardiovascular disease. Suresh serves as the organization’s founding director.

“We know mechanics plays a role in disease,” says Suresh. “We hope it can be used to figure out treatments.” If it can, the tiny field of nanomeasurement could have a huge impact on the future of medicine.