Teorijski opis uloge premosnih mikrotubula u diobenom vretenu

Autor: Bosilj, Agneza
Přispěvatelé: Pavin, Nenad
Jazyk: chorvatština
Rok vydání: 2020
Předmět:
Popis: Tijekom stanične diobe, diobeno vreteno dijeli genetski materijal u dvije identične stanice kćeri. Kinetohorni mikrotubuli u diobenom vretenu povezuju kromosome s polovima vretena i generiraju sile na kromosome putem proteinskih kompleksa zvanih kinetohore. Eksperimentalnim mjerenjima uočeni su premosni mikrotubuli koji su stabilno vezani za kinetohorne mikrotubule te su u ovom radu razvijeni fizikalni modeli koji razjašnjavaju njihovu ulogu tijekom stanične diobe. Uz kinetohorne i premosne mikrotubule i kinetohore, pri izradi modela uključena je interakcija mikrotubula s polovima diobenog vretena te pasivni i aktivni molekularni motori koji lateralno povezuju kinetohorne i premosne mikrotubule i omogućuju njihovo klizanje te aktivni motori koji reguliraju dinamiku mikrotubula. Za slučaj staničnog sustava koji se nalazi u metafazi, rješenja modela pokazuju da aktivni motori na plus krajevima mikrotubula, reguliraju prijelaz mikrotubula iz faze rasta u fazu skraćivanja te time ograničavaju kretanje kinetohora na središnju trećinu diobenog vretena. Model predviđa da stohastički član u modelu osigurava robustnost pri kretanju kinetohora za veliki raspon parametara. Također, za slučaj metafaznog diobeog vretena koje sadrži premosne mikrotubule, predviđanje je modela da će kinetohore izmaknute od središta diobenog vretena postići novi stabilni položaj koji korelira s pozicijom svežnja premosnih mikrotubula. Za slučaj sustava koji opisuje diobeno vreteno u anafazi pokazali smo da lateralno klizanje između premosnih i kinetohornih mikrotubula generirano aktivnim motorima koji se nalaze u antiparalelnim preklopima svežnjeva mikrotubula omogućuje robusnu separaciju kromosoma koja je neovisna od sila generiranih na polovu diobenog vretena. During mitosis, mitotic spindle segregates genetic material into two identical daughter cells. Kinetochore microtubules in the mitotic spindle connect the chromosomes to the spindle poles and generate forces on the chromosomes via protein complexes called kinetochores. Measurements have shown that bridging microtubules are stably bound to kinetochore microtubules and in this thesis we developed physical models that clarify their role during cell division. In addition to kinetochore microtubules, bridging microtubules and kinetochores, the model includes the interaction of microtubules with the poles of the mitotic spindle and passive and active molecular motors that laterally connect kinetochore and bridging microtubules and enable their sliding and active motors that regulate dynamics of the microtubule plus ends. For the case of a system that is in metaphase, the model solutions show that active motors at the plus ends of microtubules regulate the transition of microtubules from the growing phase to the shrinking phase and thus limit the movement of kinetochores to the central third of the mitotic spindle. The model predicts that the stochastic contribution in the model provides robustness in the motion of the kinetochore for a wide range of parameters. Also, for the case of a metaphase spindle, that contains bridging microtubules, the model predicts that the kinetochores away from the center of the spindle will achieve a new stable position that correlates with the position of the bridging microtubules overlap. For the case of a system describing the mitotic spindle in anaphase, we have shown that lateral sliding between bridging and kinetochore microtubules generated by active motors located in the antiparallel microtubule bundles allows robust chromosome separation independent of forces generated at the spindle pole.
Databáze: OpenAIRE