Innovative mechanobiology research expanding subcellular understanding, published

Advancements in regenerative medicine and developmental-biology-inspired technology, have the potential to target major human health obstacles using tissue engineering and regeneration to treat musculoskeletal, cardiac, and neural diseases, among several other known and unknown applications; however, a lack of clear understanding of the interplay between biological systems and the mechanical environment, also known as mechanobiology, has hindered research in this field, until now.

Left two images: a single beating heart cell with a high-resolution deformation map. Right two images: multiple cells displaying a muscle twitch shown with a high-resolution deformation map. The colored dots represent individual muscle nucleus. The red and blue color maps indicate the variation of deformation. Red indicates that cells are extremely tensed (pulled apart); blue indicates that cells are extremely compacted. Using deformation microscopy to view a single cell at a micro scale, it’s possible to see the deformation variation that takes place inside the cell. Image courtesy: Cell Reports

Before joining CSU in fall 2018, Dr. Soham Ghosh researched at CU Boulder with Professor Corey P. Neu and graduate student, Benjamin Seelbinder, where their mechanobiology research took off. They developed a technology called, Deformation Microscopy, capable of non-invasively probing the mechanics of the biological system in high resolution. An image-based algorithm made this possible. The results were remarkable, unhindered images of the cell, and inside the cell nucleus, exposing the missing link between biological systems and the mechanical environment.

By viewing and analyzing the cell and nucleus at high magnification, all the intricate structural architectures became visible; therefore, researchers were able to understand spatially detailed and dynamic cell deformation, which subsequently revealed how the subcellular and subnuclear regions behave in a normal physiological setting, versus a diseased setting.

Mechanical probing in biology has been prevalent for almost two decades, however, previous technologies were invasive, disturbing the physiology of the cell. Deformation Microscopy produces a high-precision, microscopic image-based strain map which can quantify the affliction a cell and nucleus can sustain, revolutionizing what was previously known about mechanobiology.

The paper, authored by Ghosh, Neu, Seelbinder, and other contributors, featuring this discovery, was accepted by prestigious scientific journal, Cell Reports. “This technology can drive the field of mechanobiology at an unprecedented rate,” said lead author, Ghosh. “The technique has proven powerful in several applications and is opening new avenues of research.”

Ghosh will leverage a variation of Deformation Microscopy and other subcellular quantification modalities in his lab, the Cellular Engineering and Mechanobiology Lab, to investigate questions surrounding single cell changes in relation to stem cell function, i.e. why, despite having the same genetic code, our individual tissues are functionally different. To fully understand this topic, his lab will study the interaction between the microenvironment, epigenetics, and chromatin architectural organization of the cell nucleus. “Deformation Microscopy will take the research in my lab to new heights, and I look forward to discoveries that will soon unfold due to this groundbreaking advancement,” added Ghosh.