Scientists identify properties that enable proteins to strengthen under pressure



In a simulated actin network, actin filaments are randomly aligned before the application of pressure (left), but align after the application of pressure (right), which changes the material properties of the network. Photo credit: Scheff et al

A new rubber band will stretch, but then snap back to its original shape and size. Stretched again, it does the same. But what if the elastic was made of a material that remembers how it was stretched? Just as our bones strengthen when they are impacted, medical implants or prostheses made from such a material can adapt to environmental stresses such as those that occur during strenuous exercise.

A research team from the University of Chicago is now investigating the properties of a material found in cells that enables cells to remember and react to environmental influences. In a paper published May 14, 2021 in Soft matter, They unveiled secrets of how it works – and how it could one day form the basis for making useful materials.

Strands of protein called actin filaments function as bones within a cell, and a separate family of proteins called crosslinkers hold these bones together into a cytoskeleton. The study found that an optimal concentration of cross-linkers that bind and re-dissolve to allow actin to rearrange itself under pressure allows this skeletal framework to remember and respond to past experiences. This material memory is called hysteresis.

“Our results show that the properties of actin networks can be changed by the alignment of filaments,” said Danielle Scheff, a PhD student in the Department of Physics who conducted the research in the lab of Margaret Gardel, Horace B. Horton Professor of Physics and Molecular Engineering, the James Franck Institute, and the Institute of Biophysical Dynamics. “The material adapts to loads by becoming stronger.”

To understand how the composition of this cellular scaffold determines its hysteresis, Scheff mixed a buffer that contained actin isolated from rabbit muscle and crosslinkers isolated from bacteria. She then applied pressure to the solution with an instrument called a rheometer. When stretched in one direction, the crosslinkers allowed the actin filaments to rearrange and strengthen against subsequent pressure in the same direction.

To see how the hysteresis depended on the consistency of the solution, she mixed different concentrations of crosslinkers into the buffer.

Surprisingly, these experiments showed that the hysteresis was most pronounced at an optimal crosslinker concentration; Solutions showed increased hysteresis when adding more crosslinker, but after this optimal point the effect became less pronounced again.

“I remember the first time I was in the lab when I drew this relationship and thought something was wrong and ran to the rheometer to do more experiments to check,” Scheff said.

To better understand the structural changes, Steven Redford, a PhD student in Biophysical Sciences in the laboratories of Gardel and Aaron Dinner, Professor of Chemistry at the James Franck Institute and the Institute for Biophysical Dynamics, created a computer simulation of the protein mixture Scheff produced in the laboratory. In this computational representation, Redford exercised more systematic control over the variables than was possible in the laboratory. By varying the stability of the bonds between actin and its crosslinkers, Redford showed that breaking up the actin filaments allows them to rearrange themselves under pressure and align with the applied load, while the binding stabilizes the new alignment and gives the tissue a “memory” of it Printing supplies. Together, these simulations showed that transient connections between proteins enable hysteresis.

“People think cells are very complicated, with a lot of chemical feedback. But this is a stripped down system where you can really understand what’s possible, ”said Gardel.

The team expects that these findings, which were obtained in a material isolated from biological systems, can be transferred to other materials. For example, the use of volatile crosslinkers to bind polymer filaments could allow them to rearrange themselves like actin filaments, making synthetic materials capable of hysteresis.

“When you understand how natural materials adapt, you can translate that into synthetic materials,” said Dinner.

Cell-bone puzzle solved with supercomputers

More information:
Danielle R. Scheff et al., Actin Filament Alignment Causes Mechanical Hysteresis in Networked Networks, Soft matter (2021). DOI: 10.1039 / d1sm00412c

Provided by the University of Chicago

Quote: Scientists identify properties that allow proteins to fortify under pressure (2021, June 16), accessed June 16, 2021 from pressure.html

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