ترغب بنشر مسار تعليمي؟ اضغط هنا

Diffusible crosslinkers cause superexponential friction forces

147   0   0.0 ( 0 )
 نشر من قبل Harmen Wierenga
 تاريخ النشر 2019
  مجال البحث فيزياء
والبحث باللغة English




اسأل ChatGPT حول البحث

The mitotic spindle lies at the heart of the spatio-temporal control over cellular components during cell division. The spindle consists of microtubules, which are not only crosslinked by motor proteins but also by passive binding proteins. These passive crosslinkers stabilize the highly dynamic mitotic spindle by generating friction forces between sliding filaments. However, it remains unclear how the friction coefficient depends on the number of crosslinkers and the size of the overlap between the microtubules. Here, we use theory and computer simulations to study the friction between two filaments that are crosslinked by passive proteins, which can hop between neighboring binding sites while physically excluding each other. The simulations reveal that the movement of one microtubule relative to the other is limited by free-energy barrier crossings, causing rare and discrete jumps of the microtubule that span the distance between adjacent crosslinker binding sites. We derive an exact analytical expression for the free-energy landscape and identify the reaction coordinate that governs the relative movement, which allows us to determine the effective barrier height for the microtubule jumps. Both through simulations and reaction rate theory, we make the experimentally testable prediction that the friction between the microtubules increases superexponentially with the density of crosslinkers.



قيم البحث

اقرأ أيضاً

In many intracellular processes, the length distribution of microtubules is controlled by depolymerizing motor proteins. Experiments have shown that, following non-specific binding to the surface of a microtubule, depolymerizers are transported to th e microtubule tip(s) by diffusion or directed walk and, then, depolymerize the microtubule from the tip(s) after accumulating there. We develop a quantitative model to study the depolymerizing action of such a generic motor protein, and its possible effects on the length distribution of microtubules. We show that, when the motor protein concentration in solution exceeds a critical value, a steady state is reached where the length distribution is, in general, non-monotonic with a single peak. However, for highly processive motors and large motor densities, this distribution effectively becomes an exponential decay. Our findings suggest that such motor proteins may be selectively used by the cell to ensure precise control of MT lengths. The model is also used to analyze experimental observations of motor-induced depolymerization.
Flagella of eukaryotic cells are transient long cylindrical protrusions. The proteins needed to form and maintain flagella are synthesized in the cell body and transported to the distal tips. What `rulers or `timers a specific type of cells use to st rike a balance between the outward and inward transport of materials so as to maintain a particular length of its flagella in the steady state is one of the open questions in cellular self-organization. Even more curious is how the two flagella of biflagellates, like Chlamydomonas Reinhardtii, communicate through their base to coordinate their lengths. In this paper we develop a stochastic model for flagellar length control based on a time-of-flight (ToF) mechanism. This ToF mechanism decides whether or not structural proteins are to be loaded onto an intraflagellar transport (IFT) train just before it begins its motorized journey from the base to the tip of the flagellum. Because of the ongoing turnover, the structural proteins released from the flagellar tip are transported back to the cell body also by IFT trains. We represent the traffic of IFT trains as a totally asymmetric simple exclusion process (TASEP). The ToF mechanism for each flagellum, together with the TASEP-based description of the IFT trains, combined with a scenario of sharing of a common pool of flagellar structural proteins in biflagellates, can account for all key features of experimentally known phenomena. These include ciliogenesis, resorption, deflagellation as well as regeneration after selective amputation of one of the two flagella. We also show that the experimental observations of Ishikawa and Marshall are consistent with the ToF mechanism of length control if the effects of the mutual exclusion of the IFT trains captured by the TASEP are taken into account. Moreover, we make new predictions on the flagellar length fluctuations and the role of the common pool.
188 - Pablo Sartori , Yuhai Tu 2015
Living systems need to be highly responsive, and also to keep fluctuations low. These goals are incompatible in equilibrium systems due to the Fluctuation Dissipation Theorem (FDT). Here, we show that biological sensory systems, driven far from equil ibrium by free energy consumption, can reduce their intrinsic fluctuations while maintaining high responsiveness. By developing a continuum theory of the E. coli chemotaxis pathway, we demonstrate that adaptation can be understood as a non-equilibrium phase transition controlled by free energy dissipation, and it is characterized by a breaking of the FDT. We show that the maximum response at short time is enhanced by free energy dissipation. At the same time, the low frequency fluctuations and the adaptation error decrease with the free energy dissipation algebraically and exponentially, respectively.
156 - Yuichi Itto , Jens B. Bosse 2018
Virus capsids in interchromatin corrals of a cell nucleus are experimentally known to exhibit anomalous diffusion as well as normal diffusion, leading to the Gaussian distribution of the diffusion-exponent fluctuations over the corrals. Here, the soj ourn-time distribution of the virus capsid in local areas of the corral, i.e., probability distribution of the sojourn time characterizing diffusion in the local areas, is examined. Such an area is regarded as a virtual cubic block, the diffusion property in which is normal or anomalous. The distribution, in which the Gaussian fluctuation is incorporated, is shown to tend to slowly decay. Then, the block-size dependence of average sojourn time is discussed. A comment is also made on (non-)Markovianity of the process of moving through the blocks.
Cell polarization underlies many cellular processes, such as differentiation, migration, and budding. Many living cells, such as budding yeast and fission yeast, use cytoskeletal structures to actively transport proteins to one location on the membra ne and create a high density spot of membrane-bound proteins. Yet, the thermodynamic constraints on filament-based cell polarization remain unknown. We show by mathematical modeling that cell polarization requires detailed balance to be broken, and we quantify the free-energy cost of maintaining a polarized state of the cell. Our study reveals that detailed balance cannot only be broken via the active transport of proteins along filaments, but also via a chemical modification cycle, allowing detailed balance to be broken by the shuttling of proteins between the filament, membrane, and cytosol. Our model thus shows that cell polarization can be established via two distinct driving mechanisms, one based on active transport and one based on non-equilibrium binding. Furthermore, the model predicts that the driven binding process dissipates orders of magnitude less free-energy than the transport-based process to create the same membrane spot. Active transport along filaments may be sufficient to create a polarized distribution of membrane-bound proteins, but an additional chemical modification cycle of the proteins themselves is more efficient and less sensitive to the physical exclusion of proteins on the transporting filaments, providing insight in the design principles of the Pom1/Tea1/Tea4 system in fission yeast and the Cdc42 system in budding yeast.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا