Platelet activation mediated by diffusion of the agonist released via optical stimulus
Ezhena S. Starodubtseva, 1 Alexander E. Moskalensky, 1 1 Novosibirsk State University, Novosibirsk, Russia
Abstract
Nowadays non-invasive approaches for treating diseases become more relevant. Amongst these methods photolabile compounds are considered to be one of promising local drug delivery techniques. Our work is focused on blood platelet activation via platelet agonist adenosine diphosphate (ADP) released through the optical stimulus on its photolabile analogue. The activation is accompanied by an increase of intracellular calcium concentration, which can be traced with fluorescent dyes. In this study, to observe the effect that free ADP spreading has on cells’ activation fluorescent microscopy was used. Special laser system was developed to control the spot location and the duration of trigger pulse. Experiments showed rapid increase in cells’ fluorescence after the trigger pulse, which indicates the process of platelet activation. Fluorescence signals were the most intense near the activation spot, whereas in distant areas the growth was delayed and attenuated. In order to describe this phenomenon the computational model of the activation spreading was developed. Model considers that the concentration of free ADP after the trigger pulse has a 2-dimensional Gaussian distribution which broadens due to diffusion. Algorithm compares calculated concentration of free ADP with activation threshold which and if it exceeds the threshold then the state switches from non-activated to activated, captures the moment when it happened and modulates a fluorescent signal for each simulated cell. Suggested approach qualitatively corresponds with the experimental data.
The study was supported by the Russian Science Foundation (grant #23-75-10049)
Speaker
Starodubtseva Ezhena
NSU, Laboratory of Optics and Dynamics of Biological Systems
Russia
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