Modulation of first-passage time for gene expression via asymmetric cell division

2019 ◽  
Vol 12 (05) ◽  
pp. 1950052
Author(s):  
Kunwen Wen ◽  
Lifang Huang ◽  
Qi Wang ◽  
Jianshe Yu
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
First Passage Time ◽  
Passage Time ◽  
Exponential Growth Rate ◽  
First Passage ◽  
Division Rate ◽  
The Mean

How to balance the size of exponentially growing cells has always been a focus of biologists. Recent experiments have uncovered that the cell is divided into two daughter cells only when the level of time-keeper protein reaches a fixed threshold and cell division in prokaryote is not completely symmetric. The timing of cell division is essentially random because gene expression is stochastic, but cells seen to manage to have precise timing of cell division events. Although the inter-cellular variability of gene expression has attracted much attention, the randomness of event timing has been rarely studied. In our analysis, the timing of cell division is formulated as the first-passage time (denoted by FPT) for time-keeper protein’s level to cross a critical threshold firstly, we derive exact analytical formulae for the mean and noise of FPT based on stochastic gene expression model with asymmetric cell division. The results of numerical simulation show that the regulatory factors (division rate, newborn cell size, exponential growth rate and threshold) have significant influence on the mean and noise of FPT. We also show that both the increase of division rate and newborn cell size could reduce the mean of FPT and increase the noise of FPT, the larger the exponential growth rate is, the smaller the mean and noise of FPT will be; and the larger the threshold value is, the higher the mean of FPT is and the lower the noise is. In addition, compared with symmetric division, asymmetric division can reduce the mean of FPT and improve the noise of FPT. In summary, our results provide insight into the relationship between regulatory factors and FPT and reveal that asymmetric division is an effective mechanism to shorten the mean of FPT.

scholarly journals A mechanistic first-passage time framework for bacterial cell-division timing

2015 ◽  
Author(s):  
Khem Raj Ghusinga ◽  
Cesar Augusto Vargas-Garcia ◽  
Abhyudai Singh
Keyword(s):  
Cell Division ◽  
Fundamental Problem ◽  
First Passage Time ◽  
Experimental Studies ◽  
Size Control ◽  
Passage Time ◽  
Bacterial Cell Division ◽  
First Passage ◽  
The Mean ◽  
Cell Division Timing

How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells on average, add a fixed size (volume) from birth to division. Interestingly, this added volume differs considerably among genetically-identical newborn cells with similar sizes suggesting a stochastic component in the timing of cell-division. To mechanistically explain the adder principle, we consider a time-keeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that while the mean cell-division time decreases with increasing size of newborns, the noise in timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distributions of the added volume and the cell-division time when scaled by their respective means become invariant of the growth rate. Finally, we discuss various modifications to the proposed model that lead to deviations from the adder principle. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for size control.

First passage time for the state of exact chemical equilibrium

1980 ◽  
Vol 45 (3) ◽  
pp. 777-782 ◽  
Author(s):  
Milan Šolc
Keyword(s):  
Chemical Equilibrium ◽  
First Passage Time ◽  
Passage Time ◽  
The State ◽  
Recurrence Time ◽  
First Passage ◽  
First Order ◽  
The Mean ◽  
Passage Times ◽  
Number Of Particles

The establishment of chemical equilibrium in a system with a reversible first order reaction is characterized in terms of the distribution of first passage times for the state of exact chemical equilibrium. The mean first passage time of this state is a linear function of the logarithm of the total number of particles in the system. The equilibrium fluctuations of composition in the system are characterized by the distribution of the recurrence times for the state of exact chemical equilibrium. The mean recurrence time is inversely proportional to the square root of the total number of particles in the system.

scholarly journals Mean first-passage time of a tumor cell growth system with time delay and colored cross-correlated noises excitation

2017 ◽  
Vol 37 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Shenghong Li ◽  
Yong Huang
Keyword(s):  
Time Delay ◽  
Noise Intensity ◽  
First Passage Time ◽  
Passage Time ◽  
Mean First Passage Time ◽  
Tumor Cell Growth ◽  
First Passage ◽  
Growth System ◽  
The Mean ◽  
Correlated Noises

In this paper, the mean first-passage time of a delayed tumor cell growth system driven by colored cross-correlated noises is investigated. Based on the Novikov theorem and the method of probability density approximation, the stationary probability density function is obtained. Then applying the fastest descent method, the analytical expression of the mean first-passage time is derived. Finally, effects of different kinds of delays and noise parameters on the mean first-passage time are discussed thoroughly. The results show that the time delay included in the random force, additive noise intensity and multiplicative noise intensity play a positive role in the disappearance of tumor cells. However, the time delay included in the determined force and the correlation time lead to the increase of tumor cells.

scholarly journals Probing Protein Shelf Lives from Inverse Mean First Passage Times

2019 ◽  
Author(s):  
Vishal Singh ◽  
Parbati Biswas
Keyword(s):  
Protein Aggregation ◽  
Rate Constants ◽  
Survival Probability ◽  
First Passage Time ◽  
Passage Time ◽  
First Passage ◽  
First Order Kinetics ◽  
The Mean ◽  
Passage Times ◽  
Good Agreement

Protein aggregation is investigated theoretically via protein turnover, misfolding, aggregation and degradation. The Mean First Passage Time (MFPT) of aggregation is evaluated within the framework of Chemical Master Equation (CME) and pseudo first order kinetics with appropriate boundary conditions. The rate constants of aggregation of different proteins are calculated from the inverse MFPT, which show an excellent match with the experimentally reported rate constants and those extracted from the ThT/ThS fluorescence data. Protein aggregation is found to be practically independent of the number of contacts and the critical number of misfolded contacts. The age of appearance of aggregation-related diseases is obtained from the survival probability and the MFPT results, which matches with those reported in the literature. The calculated survival probability is in good agreement with the only available clinical data for Parkinson’s disease.<br>

Scaling of average receiving time on double-weighted polygon networks

2021 ◽  
Author(s):  
Xiaoyan Li ◽  
Yu Sun
Keyword(s):  
Iterative Method ◽  
Path Length ◽  
First Passage Time ◽  
Passage Time ◽  
Traffic Networks ◽  
Mean First Passage Time ◽  
First Passage ◽  
Specific Calculation ◽  
Calculation Process ◽  
The Mean

In this paper, we introduce a class of double-weighted polygon networks with two different meanings of weighted factors [Formula: see text] and [Formula: see text], which represent path-difficulty and path-length, respectively, based on actual traffic networks. Picking an arbitrary node from the hub nodes set as the trap node, and the double-weighted polygon networks are divided into [Formula: see text] blocks by combining with the iterative method. According to biased random walks, the calculation expression of average receiving time (ART) of any polygon networks is given by using the intermediate quantity the mean first-passage time (MFPT), which is applicable to any [Formula: see text] ([Formula: see text]) polygon networks. What is more, we display the specific calculation process and results of ART of the double-weighted quadrilateral networks, indicating that ART grows exponentially with respect to the networks order and the exponent is [Formula: see text] which grows with the product of [Formula: see text]. When [Formula: see text] increases, ART increases linearly ([Formula: see text]) or sublinearly ([Formula: see text]) with the size of networks, and the smaller value of [Formula: see text], the higher transportation efficiency.

Calculations of first passage time of delayed tree-like networks

2015 ◽  
Vol 29 (28) ◽  
pp. 1550200
Author(s):  
Shuai Wang ◽  
Weigang Sun ◽  
Song Zheng
Keyword(s):  
Random Walks ◽  
First Passage Time ◽  
Passage Time ◽  
The Novel ◽  
Mean First Passage Time ◽  
First Passage ◽  
Initial Node ◽  
Network Parameters ◽  
Self Similar ◽  
The Mean

In this paper, we study random walks in a family of delayed tree-like networks controlled by two network parameters, where an immobile trap is located at the initial node. The novel feature of this family of networks is that the existing nodes have a time delay to give birth to new nodes. By the self-similar network structure, we obtain exact solutions of three types of first passage time (FPT) measuring the efficiency of random walks, which includes the mean receiving time (MRT), mean sending time (MST) and mean first passage time (MFPT). The obtained results show that the MRT, MST and MFPT increase with the network parameters. We further show that the values of MRT, MST and MFPT are much shorter than the nondelayed counterpart, implying that the efficiency of random walks in delayed trees is much higher.

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