Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Poster Abstracts

9-POS Board 9 INTERPRETING EQUATORIAL X-RAY DIFFRACTION PATTERNS FROM STRIATED MUSCLE WITH MULTISCALE MODELING Momcilo Prodanovic 1 ; Yiwei Wang 3 ; Srboljub Mijailovich 2 ; Thomas C. Irving 3 ; 1 University of Kragujevac, Institute for Information Technologies, Kragujevac, Serbia 2 FilamenTech, Inc, Newton, MA, USA 3 Illinois Insitute of Technology, Biology, Chicago, IL, USA Synchrotron small-angle X-ray diffraction is the method of choice for nm-scale structural studies of striated muscle under physiological conditions and on millisecond time-scales. The lack of generally applicable computational tools for modeling X-ray diffraction patterns from intact muscles have been a significant barrier to exploiting the full potential of this technique. Here we report a novel, “forward problem” approach using the spatially explicit computational simulation platform, MUSICO, to predict equatorial small angle X-ray diffraction patterns and the force output simultaneously from resting and isometrically contracting rat skeletal muscle that can be compared to experimental data. The simulation generates families of thick-thin filament repeating units each with their individually predicted occupancies of different populations of active and inactive myosin heads that can be used to generate 2D projected electron density models based on known Protein Data Bank structures. Using this approach, we found that we could recapitulate 7 independent experimental intensities (out to the 4,0 reflection) from relaxed rat soleus and EDL muscle by varying only the proportion of heads in the parked state and a temperature factor type disorder term. Fits to contracting data could be achieved by adjusting only the temperature factor term and the number of force-producing crossbridges predicted by MUSICO to match the force levels observed experimentally. The developments presented here demonstrate the feasibility of combining X-ray diffraction and spatially explicit modeling to form a powerful hypothesis generating tool that can be used to motivate experiments that can reveal emergent properties of muscle. Supported by NIH and the AHA.

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