This book covers recent developments in the non-standard asymptotics of the mathematical narrow escape problem in stochastic theory, as well as applications of the narrow escape problem in cell biology. The first part of the book concentrates on mathematical methods, including advanced asymptotic methods in partial equations, and is aimed primarily at applied mathematicians and theoretical physicists who are interested in biological applications. The second part of the book is intended for computational biologists, theoretical chemists, biochemists, biophysicists, and physiologists. It includes a summary of output formulas from the mathematical portion of the book and concentrates on their applications in modeling specific problems in theoretical molecular and cellular biology. Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small spatial scales. These may be small binding sites inside or on the surface of the cell, or narrow passages between subcellular compartments. The great disparity in spatial scales is the key to controlling cell function by structure. This volume reports recent progress on resolving analytical and numerical difficulties in extracting properties from experimental data, biophysical models, and from Brownian dynamics simulations of diffusion in multi-scale structures.

This book develops the theory of continuous and discrete stochastic processes within the context of cell biology. In the second edition the material has been significantly expanded, particularly within the context of nonequilibrium and self-organizing systems. Given the amount of additional material, the book has been divided into two volumes, with volume I mainly covering molecular processes and volume II focusing on cellular processes. A wide range of biological topics are covered in the new edition, including stochastic ion channels and excitable systems, molecular motors, stochastic gene networks, genetic switches and oscillators, epigenetics, normal and anomalous diffusion in complex cellular environments, stochastically-gated diffusion, active intracellular transport, signal transduction, cell sensing, bacterial chemotaxis, intracellular pattern formation, cell polarization, cell mechanics, biological polymers and membranes, nuclear structure and dynamics, biological condensates, molecular aggregation and nucleation, cellular length control, cell mitosis, cell motility, cell adhesion, cytoneme-based morphogenesis, bacterial growth, and quorum sensing. The book also provides a pedagogical introduction to the theory of stochastic and nonequilibrium processes – Fokker Planck equations, stochastic differential equations, stochastic calculus, master equations and jump Markov processes, birth-death processes, Poisson processes, first passage time problems, stochastic hybrid systems, queuing and renewal theory, narrow capture and escape, extreme statistics, search processes and stochastic resetting, exclusion processes, WKB methods, large deviation theory, path integrals, martingales and branching processes, numerical methods, linear response theory, phase separation, fluctuation-dissipation theorems, age-structured models, and statistical field theory. This text is primarily aimed at graduate students and researchers working in mathematical biology, statistical and biological physicists, and applied mathematicians interested in stochastic modeling. Applied probabilists should also find it of interest. It provides significant background material in applied mathematics and statistical physics, and introduces concepts in stochastic and nonequilibrium processes via motivating biological applications. The book is highly illustrated and contains a large number of examples and exercises that further develop the models and ideas in the body of the text. It is based on a course that the author has taught at the University of Utah for many years.

This book focuses on the modeling and mathematical analysis of stochastic dynamical systems along with their simulations. The collected chapters will review fundamental and current topics and approaches to dynamical systems in cellular biology. This text aims to develop improved mathematical and computational methods with which to study biological processes. At the scale of a single cell, stochasticity becomes important due to low copy numbers of biological molecules, such as mRNA and proteins that take part in biochemical reactions driving cellular processes. When trying to describe such biological processes, the traditional deterministic models are often inadequate, precisely because of these low copy numbers. This book presents stochastic models, which are necessary to account for small particle numbers and extrinsic noise sources. The complexity of these models depend upon whether the biochemical reactions are diffusion-limited or reaction-limited. In the former case, one needs to adopt the framework of stochastic reaction-diffusion models, while in the latter, one can describe the processes by adopting the framework of Markov jump processes and stochastic differential equations. Stochastic Processes, Multiscale Modeling, and Numerical Methods for Computational Cellular Biology will appeal to graduate students and researchers in the fields of applied mathematics, biophysics, and cellular biology.

This book develops the theory of continuous and discrete stochastic processes within the context of cell biology. In the second edition the material has been significantly expanded, particularly within the context of nonequilibrium and self-organizing systems. Given the amount of additional material, the book has been divided into two volumes, with volume I mainly covering molecular processes and volume II focusing on cellular processes. A wide range of biological topics are covered in the new edition, including stochastic ion channels and excitable systems, molecular motors, stochastic gene networks, genetic switches and oscillators, epigenetics, normal and anomalous diffusion in complex cellular environments, stochastically-gated diffusion, active intracellular transport, signal transduction, cell sensing, bacterial chemotaxis, intracellular pattern formation, cell polarization, cell mechanics, biological polymers and membranes, nuclear structure and dynamics, biological condensates, molecular aggregation and nucleation, cellular length control, cell mitosis, cell motility, cell adhesion, cytoneme-based morphogenesis, bacterial growth, and quorum sensing. The book also provides a pedagogical introduction to the theory of stochastic and nonequilibrium processes – Fokker Planck equations, stochastic differential equations, stochastic calculus, master equations and jump Markov processes, birth-death processes, Poisson processes, first passage time problems, stochastic hybrid systems, queuing and renewal theory, narrow capture and escape, extreme statistics, search processes and stochastic resetting, exclusion processes, WKB methods, large deviation theory, path integrals, martingales and branching processes, numerical methods, linear response theory, phase separation, fluctuation-dissipation theorems, age-structured models, and statistical field theory. This text is primarily aimed at graduate students and researchers working in mathematical biology, statistical and biological physicists, and applied mathematicians interested in stochastic modeling. Applied probabilists should also find it of interest. It provides significant background material in applied mathematics and statistical physics, and introduces concepts in stochastic and nonequilibrium processes via motivating biological applications. The book is highly illustrated and contains a large number of examples and exercises that further develop the models and ideas in the body of the text. It is based on a course that the author has taught at the University of Utah for many years.

This is a monograph on the emerging branch of mathematical biophysics combining asymptotic analysis with numerical and stochastic methods to analyze partial differential equations arising in biological and physical sciences. In more detail, the book presents the analytic methods and tools for approximating solutions of mixed boundary value problems, with particular emphasis on the narrow escape problem. Informed throughout by real-world applications, the book includes topics such as the Fokker-Planck equation, boundary layer analysis, WKB approximation, applications of spectral theory, as well as recent results in narrow escape theory. Numerical and stochastic aspects, including mean first passage time and extreme statistics, are discussed in detail and relevant applications are presented in parallel with the theory. Including background on the classical asymptotic theory of differential equations, this book is written for scientists of various backgrounds interested in deriving solutions to real-world problems from first principles.

Processes involving randomly moving particles, which react either upon encounter or via distance-dependent reaction rates, are ubiquitous in nature. A few stray examples are recombination of ions or holes and electrons, excitation energy migration and quenching, trapping of particles by other species, coagulation, binding of ligands and proteins to specific sites, chemotaxis, catalytically-induced self-propulsion, polymerization, growth of dendrites or aggregates, or nuclei of a new phase.Several decades ago, it was recognized that the kinetic behavior in some systems with reactions and random transport is strongly affected by many factors, which were not taken into account in previous studies. These are, to name but a few, fluctuations in the spatial distributions of the reactants and fluctuations of the reactivity, some essentially many-particle phenomena, effects of anomalous diffusion, molecular crowding, as well as the internal geometry of the reaction bath. Within recent years, along with a growing interest in chemical processes ocurring in biological systems or cellular environments, numerous advances have been made and considerable knowledge has been acquired. These seminal contributions are, however, scattered among many journals and no attempt has been made so far to present a unified picture.This book presents a general overview of different contemporary facets of chemical kinetics in a variety of different environments. It includes 23 seminal works and reviews on different aspects of reaction processes in chemical, physical and biophysical systems, both theoretical and experimental.

Any brain activity relies on the interaction of thousands of neurons, each of which integrating signals from thousands of synapses. While neurons are undoubtedly the building blocks of the brain, synapses constitute the main loci of information transfer that lead to the emergence of neuronal code. Investigating synaptic transmission constitutes a multi-faceted challenge that brings together a large number of techniques and expertise ranging from experimental to computational approaches, bringing together paradigms spanning from molecular to neural network level. In this book, we have collected a series of articles that present foundational work aimed at shedding much-needed light on brain information processing, synaptic transmission and neural code formation. Some articles present analyses of regulatory mechanisms underlying neural code formation and its elaboration at the molecular level, while others use computational and modelling approaches to investigate, at synaptic, neuronal and inter-neuronal level, how the different mechanisms involved in information processing interact to generate effects like long-term potentiation (LTP), which constitutes the cellular basis of learning and memory. This collection, although not exhaustive, aims to present a framework of the most used investigational paradigms and showcase results that may, in turn, generate novel hypotheses and ideas for further studies and investigations.