Cooperative protein transport in cellular organelles

Compartmentalization into biochemically distinct organelles constantly exchanging material is one of the hallmarks of eukaryotic cells. In the most naive picture of inter-organelle transport driven by concentration gradients, concentration differences between organelles should relax. We determine the conditions under which cooperative transport, i.e. based on molecular recognition, allows for the existence and maintenance of distinct organelle identities. Cooperative transport is also shown to control the flux of material transiting through a compartmentalized system, dramatically increasing the transit time under high incoming flux. By including chemical processing of the transported species, we show that this property provides a strong functional advantage to a system responsible for protein maturation and sorting.Comment: 9 pages, 5 figure

Functional Genomics of Brain Aging and Alzheimer’s Disease: Focus on Selective Neuronal Vulnerability

Pivotal brain functions, such as neurotransmission, cognition, and memory, decline with advancing age and, especially, in neurodegenerative conditions associated with aging, such as Alzheimer’s disease (AD). Yet, deterioration in structure and function of the nervous system during aging or in AD is not uniform throughout the brain. Selective neuronal vulnerability (SNV) is a general but sometimes overlooked characteristic of brain aging and AD. There is little known at the molecular level to account for the phenomenon of SNV. Functional genomic analyses, through unbiased whole genome expression studies, could lead to new insights into a complex process such as SNV. Genomic data generated using both human brain tissue and brains from animal models of aging and AD were analyzed in this review. Convergent trends that have emerged from these data sets were considered in identifying possible molecular and cellular pathways involved in SNV. It appears that during normal brain aging and in AD, neurons vulnerable to injury or cell death are characterized by significant decreases in the expression of genes related to mitochondrial metabolism and energy production. In AD, vulnerable neurons also exhibit down-regulation of genes related to synaptic neurotransmission and vesicular transport, cytoskeletal structure and function, and neurotrophic factor activity. A prominent category of genes that are up-regulated in AD are those related to inflammatory response and some components of calcium signaling. These genomic differences between sensitive and resistant neurons can now be used to explore the molecular underpinnings of previously suggested mechanisms of cell injury in aging and AD

Single Molecule Michaelis-Menten Equation beyond Quasi-Static Disorder

The classic Michaelis-Menten equation describes the catalytic activities for ensembles of enzyme molecules very well. But recent single-molecule experiment showed that the waiting time distribution and other properties of single enzyme molecule are not consistent with the prediction based on the viewpoint of ensemble. It has been contributed to the slow inner conformational changes of single enzyme in the catalytic processes. In this work we study the general dynamics of single enzyme in the presence of dynamic disorder. We find that at two limiting cases, the slow reaction and nondiffusion limits, Michaelis-Menten equation exactly holds although the waiting time distribution has a multiexponential decay behaviors in the nondiffusion limit.Particularly, the classic Michaelis-Menten equation still is an excellent approximation other than the two limits.Comment: 10 pages, 1 figur

Entropy driven key-lock assembly

The effective interaction between a sphere with an open cavity (lock) and a spherical macroparticle (key), both immersed in a hard sphere fluid, is studied by means of Monte Carlo simulations. As a result, a 2d map of the key-lock effective interaction potential is constructed, which leads to the proposal of a self-assembling mechanism: there exists trajectories through which the key-lock pair could assemble avoiding trespassing potential barriers. Hence, solely the entropic contribution can induce their self-assembling even in the absence of attractive forces. This study points out the solvent contribution within the underlying mechanisms of substrate-protein assembly/disassembly processes, which are important steps of the enzyme catalysis and protein mediated transport

Non-equilibrium dynamics of gene expression and the Jarzynski equality

In order to express specific genes at the right time, the transcription of genes is regulated by the presence and absence of transcription factor molecules. With transcription factor concentrations undergoing constant changes, gene transcription takes place out of equilibrium. In this paper we discuss a simple mapping between dynamic models of gene expression and stochastic systems driven out of equilibrium. Using this mapping, results of nonequilibrium statistical mechanics such as the Jarzynski equality and the fluctuation theorem are demonstrated for gene expression dynamics. Applications of this approach include the determination of regulatory interactions between genes from experimental gene expression data

Living on the edge of chaos: minimally nonlinear models of genetic regulatory dynamics

Linearized catalytic reaction equations modeling e.g. the dynamics of genetic regulatory networks under the constraint that expression levels, i.e. molecular concentrations of nucleic material are positive, exhibit nontrivial dynamical properties, which depend on the average connectivity of the reaction network. In these systems the inflation of the edge of chaos and multi-stability have been demonstrated to exist. The positivity constraint introduces a nonlinearity which makes chaotic dynamics possible. Despite the simplicity of such minimally nonlinear systems, their basic properties allow to understand fundamental dynamical properties of complex biological reaction networks. We analyze the Lyapunov spectrum, determine the probability to find stationary oscillating solutions, demonstrate the effect of the nonlinearity on the effective in- and out-degree of the active interaction network and study how the frequency distributions of oscillatory modes of such system depend on the average connectivity.Comment: 11 pages, 5 figure