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Ramsukh, M.

Publications and source records attributed to Ramsukh, M..

2 recordsLinked to original sources

Determining the Youngs Modulus of the Bacterial Cell Envelope

Bacteria experience substantial physical forces in their natural environment including forces caused by osmotic pressure, growth in constrained spaces, and fluid shear. The cell envelope is the primary load-carrying structure of bacteria, but the mechanical properties of the cell envelope are poorly understood; reports of Youngs modulus of the cell envelope of E. coli are widely range from 2 MPa to 18 MPa. We have developed a microfluidic system to apply mechanical loads to hundreds of bacteria at once and demonstrated the utility of the approach for evaluating whole-cell stiffness. Here we extend this technique to determine Youngs modulus of the cell envelope of E. coli and of the pathogens V. cholerae and S. aureus. An optimization-based inverse finite element analysis was used to determine the cell envelope Youngs modulus from observed deformations. The Youngs modulus of the cell envelope was 2.06 {+/-} 0.04 MPa for E. coli, 0.84 {+/-} 0.02 MPa for E. coli treated with a chemical known to reduce cell stiffness, 0.12 {+/-} 0.03 MPa for V. cholerae, and 1.52 {+/-} 0.06 MPa for S. aureus (mean {+/-} SD). The microfluidic approach allows examining hundreds of cells at once and is readily applied to Gram-negative and Gram-positive organisms as well as rod-shaped and cocci cells, allowing further examination of the structural causes of differences in cell envelope Youngs modulus among bacteria species and strains.

bioengineering↗

Adult Hox gene expression promotes periosteal stem cell maintenance and mediates reprogramming in a regionally restricted manner

Periosteal stem and progenitor cells are pivotal to the growth and lifelong turnover of bone and underpin its capacity to regenerate. Adjusting the potency of this cell population will therefore be critical to the successful generation and application of new bone repair therapies. Following their role in patterning the embryonic skeleton, Hox genes remain regionally expressed in mesenchymal stromal cell populations of the adult skeleton. Here we show that Hoxa10 is most expressed in the most uncommitted periosteal stem cell and that Hox maintains these skeletal stem cells in a multipotential, uncommitted state, thereby preventing their differentiation into bone. We demonstrate that Hoxa10 mediates the reprogramming of periosteal progenitors towards a stem cell state with greater self-renewal capacity and also establish that region-specific Hox genes mediate cell reprogramming in distinct anatomical regions, demonstrating the continued functional relevance of the embryonic Hox profile in adult stem cells. Together, our data describe a master regulator role of Hox in skeletal stem and progenitor cells and help provide insight into the development of cell-based therapies for treatment of at-risk bone fractures and other bone-related ailments.

molecular biology↗