Meredys, a multi-compartment reaction-diffusion simulator using multistate realistic molecular complexes

<p>Abstract</p> <p>Background</p> <p>Most cellular signal transduction mechanisms depend on a few molecular partners whose roles depend on their position and movement in relation to the input signal. This movement can follow various rules and take place in different compartments. Additionally, the molecules can form transient complexes. Complexation and signal transduction depend on the specific states partners and complexes adopt. Several spatial simulator have been developed to date, but none are able to model reaction-diffusion of realistic multi-state transient complexes.</p> <p>Results</p> <p><it>Meredys </it>allows for the simulation of multi-component, multi-feature state molecular species in two and three dimensions. Several compartments can be defined with different diffusion and boundary properties. The software employs a Brownian dynamics engine to simulate reaction-diffusion systems at the reactive particle level, based on compartment properties, complex structure, and hydro-dynamic radii. Zeroth-, first-, and second order reactions are supported. The molecular complexes have realistic geometries. Reactive species can contain user-defined feature states which can modify reaction rates and outcome. Models are defined in a versatile NeuroML input file. The simulation volume can be split in subvolumes to speed up run-time.</p> <p>Conclusions</p> <p><it>Meredys </it>provides a powerful and versatile way to run accurate simulations of molecular and sub-cellular systems, that complement existing multi-agent simulation systems. <it>Meredys </it>is a Free Software and the source code is available at <url>http://meredys.sourceforge.net/</url>.</p

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

CA2+ IMAGING PRINCIPLES OF ANALYSIS AND ENHANCEMENT

In this chapter, we review the theoretical and experimental foundations underling a quantitative approach to Ca2+ imaging, discuss equilibrium conditions and their violations and present a computational framework that can be used to estimate the spatial and temporal dynamics of Ca2+ signals based of fluorescence measurements with Ca2+ indicators