During the cell cycle, the organization of the cytoskeletal network undergoes dramatic changes. In order to reveal possible changes of the viscoelastic properties in the intracellular space during the cell cycle we investigated the diffusion of endogenous lipid granules within the fission yeast Schizosaccharomyces Pombe using optical tweezers. The cell cycle was divided into interphase and mitotic cell division, and the mitotic cell division was further subdivided in its stages. During all stages of the cell cycle, the granules predominantly underwent subdiffusive motion, characterized by an exponent alpha that is also linked to the viscoelastic moduli of the cytoplasm. The exponent alpha was significantly smaller during interphase than during any stage of the mitotic cell division, signifying that the cytoplasm was more elastic during interphase than during division. We found no significant differences in the subdiffusive exponents from granules measured in different stages of cell division. Also, our results for the exponent displayed no significant dependence on the position of the granule within the cell. The observation that the cytoplasm is more elastic during interphase than during mitotic cell division is consistent with the fact that elastic cytoskeletal elements such as microtubules are less abundantly present during cell division than during interphase.
BackgroundWaves propagating in "excitable media" is a reliable way to transmit signals in space. A fascinating example where living cells comprise such a medium is Dictyostelium D. which propagates waves of chemoattractant to attract distant cells. While neutrophils chemotax in a similar fashion as Dictyostelium D., it is unclear if chemoattractant waves exist in mammalian tissues and what mechanisms could propagate them.ResultsWe propose that chemoattractant cytokine waves may naturally develop as a result of NF-κB response. Using a heuristic mathematical model of NF-κB-like circuits coupled in space we show that the known characteristics of NF-κB response favor cytokine waves.ConclusionsWhile the propagating wave of cytokines is generally beneficial for inflammation resolution, our model predicts that there exist special conditions that can cause chronic inflammation and re-occurrence of acute inflammatory response.
A number of different proteins possess the ability to polymerize into filamentous structures. Certain classes of such assemblies can have key functional roles in the cell, such as providing the structural basis for the cytoskeleton in the case of actin and tubulin, while others are implicated in the development of many pathological conditions, including Alzheimer's and Parkinson's diseases. In general, the fragmentation of such structures changes the total number of filament ends, which act as growth sites, and hence is a key feature of the dynamics of filamentous growth phenomena. In this paper, we present an analytical study of the master equation of breakable filament assembly and derive closed-form expressions for the time evolution of the filament length distribution for both open and closed systems with infinite and finite monomer supply, respectively. We use this theoretical framework to analyse experimental data for length distributions of insulin amyloid fibrils and show that our theory allows insights into the microscopic mechanisms of biofilament assembly to be obtained beyond those available from the conventional analysis of filament mass only.
The regulatory system of the transcription factor NF-κB plays a great role in many cell functions, including inflammatory response. Interestingly, the NF-κB system is known to up-regulate production of its own triggering signal-namely, inflammatory cytokines such as TNF, IL-1, and IL-6. In this paper we investigate a previously presented model of the NF-κB, which includes both spatial effects and the positive feedback from cytokines. The model exhibits the properties of an excitable medium and has the ability to propagate waves of high cytokine concentration. These waves represent an optimal way of sending an inflammatory signal through the tissue as they create a chemotactic signal able to recruit neutrophils to the site of infection. The simple model displays three qualitatively different states; low stimuli leads to no or very little response. Intermediate stimuli leads to reoccurring waves of high cytokine concentration. Finally, high stimuli leads to a sustained high cytokine concentration, a scenario which is toxic for the tissue cells and corresponds to chronic inflammation. Due to the few variables of the simple model, we are able to perform a phase-space analysis leading to a detailed understanding of the functional form of the model and its limitations. The spatial effects of the model contribute to the robustness of the cytokine wave formation and propagation.
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