Reaction rates estimation for the endocytic reception in extracellular vesicles-mediated communications

Abstract

The extracellular vesicles (EVs) role in intercellular communication of transferring the cargoes of biomolecules such as proteins and nucleic acid between cells has been revealed recently. EV-mediated molecular communications (MC) is involved in targeted cells that receive EVs following the mechanisms of endocytosis. Such mechanisms comprise various processes of EV binding, internalization, and recycling that are characterized by specific factors of reaction. Accurate estimation of these factors is essential for the MC receiver assessment upon EV signaling. Here, we propose a fitting model to approximate the reaction rate parameters based on a suggested scenario corresponding to an experimental setup. The results of relative error for the estimated rates based on the simulated data are presented. The estimation method given in this paper can help future works on data analysis and minimizing the experimental resources. CCS CONCEPTS• Applied computing → Computational biology; Health care information systems; Physical sciences and engineering.

Computational estimation of chemical reaction rates in extracellular vesicle signaling

“…Figure 7 shows that over-or underestimation mainly affects the NMSEE of k b . This observation is consistent with previous analysis [5]. The reason is that the binding process described by k b is directly influenced by Q 0 , while k r and k i depend only on the bound EVs.…”

“…Values of chemical reactions involved in EV transport yield information about the reaction's mechanism and transition states, and are critical for the creation of mathematical models that are used as a tool to describe the characteristics of EV transport. Moreover, such values are essential for prototyping EV-based therapy [5,6], for example, anticancer therapy [7], giving insights into how fast the biomolecule-carrying EV absorption occurs or what is the survival rate of cancer cells that is closely dependent on the rate and amount of the received biomolecules. Furthermore, values of chemical reactions are important for effectively establishing a communication link between bio-transceivers in an EV-based communication network [8,9].…”

“…We have recently proposed a computational approach which, in combination with a simple experimental setup, can be utilized for the estimation of chemical rates associated with the EV uptake [5]. In the experimental setup, the cells are cultured in multiple wells and then mixed with a known concentration of EVs, as illustrated in Figure 2.…”

“…Different wells are used for different time-points of data acquisition where only the EVs present in the medium were quantified by NTA; in this regard, the time-course of the environmental EVs could be characterized. The suggested computational approach is based on a closed-form fitting function derived from ordinary differential equations (ODEs) that correspond to the kinetic model of EV uptake [5]. The suggested model, however, does not consider the number of available binding sites on the cell membrane which is a critical factor in the receptor-mediated endocytotic pathway of EV uptake.…”

“…In addition, we extend our previous linear system model based solution in [5] by deriving closed-form expressions for rate estimation which avoids computationally complex curve fitting. Moreover, we suggest computing the reaction rates by applying Michaelis-Menten kinetics directly in the frequency domain under the pseudo-steady-state assumption.…”