diff --git a/tex/thesis.tex b/tex/thesis.tex index f8ecda2..982a06d 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -4659,7 +4659,91 @@ hosted using \gls{aws} using their proprietary Aurora implementation. The code is available here: \url{https://github.gatech.edu/ndwarshuis3/mdma}. -\chapter{BINDING KINETICS CODE}\label{sec:appendix_binding} +\chapter{BINDING KINETICS}\label{sec:appendix_binding} + +\newcommand{\lig}{\textit{ligand}} +\newcommand{\rcp}{\textit{receptor}} +\newcommand{\ligs}{\textit{ligands}} +\newcommand{\rcps}{\textit{receptors}} + +To model binding kinetics of either \gls{stp} or \glspl{mab} (here called +\ligs{}), each microcarrier was assumed to be a porous sphere with a given +number of binding sites for the \ligs{} (here called \rcps{}). The \rcp{}/\lig{} +reaction was assumed to be instantaneous (which is reasonable given that these +are reactions between biotin and \gls{stp} which are extremely strong). From +this, we further assumed a spherical interface within each microcarrier and +aligned at the center wherein all \rcps{} in the interior were unbound and all +on the exterior were bound. At $t=0$ this interface was assumed to start with a +radius equal to that of the microcarrier, and shrunk down to radius of zero as +\ligs{} flowed into the porous microcarriers and bound. We assumed the +concentration of \lig{} to be zero at the interface and equal to the bulk +concentration at the exterior surface of the microcarrier. Furthermore, we +assumed that the interface move slowly relative to the diffusion of \lig{} into +the microcarriers, and thus we used a quasi-steady-state model to avoid solving +a boundary value problem with two movable boundaries (the interface radius and +the concentration in bulk). + +The concentration profile of \lig{} in the microcarriers is given by Fick's +Second Law in spherical coordinates assuming only radial flux and steady state. +This with the boundary conditions as stated is: + +\begin{equation} + \label{eqn:binding_ficks} + 0 = \frac{1}{r^2}\frac{d}{dr}\left(r^2\frac{dC_L}{dr}\right) +\end{equation} + +\begin{equation} + \label{eqn:binding_bc_left} + C_L\rvert_{r_i} = 0 +\end{equation} + +\begin{equation} + \label{eqn:binding_bc_right} + C_L\rvert_R = C_{L,b} +\end{equation} + +Solving \cref{eqn:binding_ficks} we find the a relation for the concentration +profile in terms of the interfacial radius: + +\begin{equation} + \label{eqn:binding_conc} + C_L = \frac{C_{L,b}}{r(1/r_i - 1/R)}\left(\frac{1}{r_i} - \frac{1}{r}\right) +\end{equation} + +Solving \cref{eqn:binding_conc} for flux, the molar flow rate into the +microcarriers is given by: + +\begin{equation} + \label{eqn:binding_molar_flow} + Q = 4\pi R^2N\rvert_R = \frac{-4\pi DC}{1/r_i - 1/R} +\end{equation} + +Using the quasi-steady-state assumption, we can now find time-dependent +equations for the interfatial radius and the bulk concentration. The interfacial +volume in terms of molar flow rate is given by: + +\begin{equation} + \label{eqn:binding_volume_change} + C_{R,0}\frac{dV_i}{dt} = -Q +\end{equation} + +Substituting volume of a sphere and applying the chain rule: + +\begin{equation} + \label{eqn:radial_radial_change} + \frac{dr_i}{dt} = \frac{-Q}{4\pi r_i^2C_{R,0}} +\end{equation} + +The change in bulk concentration is simply given by: + +\begin{equation} + \label{eqn:radial_conc_change} + \frac{dC_{L,b}}{dt} = \frac{-nQ}{V} +\end{equation} + +Substituting \cref{eqn:binding_molar_flow} into \cref{eqn:radial_radial_change} +and \cref{eqn:radial_conc_change} yields \cref{eqn:stp_diffusion_1} and +\cref{eqn:stp_diffusion_2}. The \gls{stp} binding kinetic profile was fit and calculated using the following MATLAB code. Note that the \inlinecode{geometry} parameter was varied so as to