MIT engineers have devised a brand new, noninvasive technique to measure the stiffness of residing cells utilizing acoustic waves. Their approach permits them to watch single cells over a number of generations and examine how stiffness modifications as cells undergo the cell division cycle.
This method is also used to check different organic phenomena reminiscent of programmed cell loss of life or metastasis, the researchers say.
“Noninvasive monitoring of single-cell mechanical properties might be helpful for finding out many several types of mobile processes,” says Scott Manalis, the Andrew and Erna Viterbi Professor within the MIT departments of Organic Engineering and Mechanical Engineering, a member of MIT’s Koch Institute for Integrative Most cancers Analysis, and the senior writer of the examine.
It is also helpful for analyzing how sufferers’ tumor cells reply to sure medicine, doubtlessly serving to medical doctors select the most effective medicine for particular person sufferers, the researchers say.
Joon Ho Kang, an MIT graduate scholar, is the primary writer of the paper, which seems within the Feb. 11 problem of Nature Strategies. Different authors embrace postdocs Teemu Miettinen and Georgios Katsikis, graduate scholar Lynna Chen, visiting scholar Selim Olcum, and professor of chemical engineering Patrick Doyle.
A novel measurement
The brand new measurement approach makes use of a know-how that Manalis’ lab beforehand developed to measure the mass of cells. This system, generally known as the suspended microchannel resonator (SMR), can measure the mass of cells as they move by a tiny fluid-filled cantilever that vibrates inside a vacuum cavity. As cells move by the channel, their mass barely alters the cantilever’s vibration frequency, and the mass of the cell might be calculated from that change in frequency.
Within the new examine, the researchers found that they may additionally measure modifications in stiffness to the cell — particularly, a cell construction referred to as the cortex that lies slightly below the cell membrane. The cortex, which helps to find out the form of a cell, consists primarily of actin filaments. Contraction and leisure of those filaments usually happens throughout processes reminiscent of cell division, metastasis, and programmed cell loss of life, resulting in modifications within the stiffness of the cortex.
Over the previous couple of years, Manalis and his college students realized that the vibration of the cantilever additionally creates an acoustic wave that can be utilized to measure the stiffness of the particle or cell flowing by the system. As a particle flows by the channel, it interacts with the acoustic waves, altering the general power steadiness. This alters the vibration of the cantilever, by an quantity that varies relying on stiffness of the cell or particle. This enables the researchers to calculate the stiffness of the cell by measuring how a lot the vibration modifications.
The researchers confirmed that their approach is correct by measuring hydrogel particles of recognized stiffnesses, created in Doyle’s lab, and measuring them as they flowed by the system.
The acoustic waves used to generate these measurements disturb the cell by solely about 15 nanometers, a lot lower than the displacement produced by most present strategies for measuring mechanical properties.
The MIT workforce confirmed that they may use this method to measure stiffness of a single cell repeatedly for over 20 hours as they flowed forwards and backwards by the SMR system. Throughout this time, they have been capable of monitor stiffness by two or extra cell division cycles. They discovered that as cells enter mitosis, stiffness decreases, which the researchers imagine is as a result of swelling that happens when the cells put together to divide. By imaging the cells, they confirmed that the cell cortex turns into thinner because the cell swells.
The researchers additionally discovered that cell stiffness dynamically modifications simply earlier than it divides. Actin accumulates on the equatorial area, making the cell stiffer, whereas the polar areas change into extra relaxed as actins are briefly depleted.
“We will use our method of measuring stiffness to have a look at the dynamics of actin in a label-free, noninvasive method,” Kang says.
The researchers plan to start out utilizing this method to measure the stiffness of even smaller particles, reminiscent of viruses, and to discover whether or not that measurement is likely to be correlated with a virus’s infectivity.
“Measuring stiffness of submicron particles with significant throughput is presently not potential with present approaches,” Manalis says. Such a functionality might assist researchers who’re engaged on growing weakened viruses that might be examined as potential vaccines. This type of measurement is also used to assist characterize tiny particles reminiscent of these used for drug supply.
One other potential utility is combining the stiffness measurement with the mass and progress charge measurements that Manalis’ lab has been growing as a potential predictor of how particular person most cancers sufferers will reply to explicit medicine.
“In the case of assays for precision drugs, measuring a number of practical properties from the identical cell might assist to make assessments extra predictive,” Manalis says.
The analysis was funded by the Koch Institute Assist Grant from the Nationwide Most cancers Institute (NCI), the Ludwig Heart for Molecular Oncology, the NCI Most cancers Methods Biology Consortium, and the Institute for Collaborative Biotechnologies by the U.S. Military Analysis Workplace.