Uloga premosnih mikrotubula u ravnoteži sila diobenog vretena

doctoral thesis

• Title (english): The role of bridging microtubules in the force balance of mitotic spindle
• Author: Maja Novak
• Mentor: Nenad Pavin (mentor)
• Committee member: Antonio Šiber (predsjednik povjerenstva)
• Committee member: Nenad Pavin (član povjerenstva)
• Committee member: Igor Weber (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Physics); Zagreb
• Defense date and country: 2017-10-03, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Physics
• Universal decimal classification (UDC): 53 - Physics

Abstract

Tijekom stanične diobe, genetski materijal stanice se precizno dijeli u dvije stanice kćeri, cime mehanički i biološki upravlja mreža proteinskih filamenata koju nazivamo diobeno vreteno. Poznato je da ti proteinski filamenti, mikrotubuli, imaju elastična svojstva. Skupina mikrotubula, koju nazivamo kinetohorni mikrotubuli, djeluje silom tenzije na kromosome. Kinetohore su proteinski kompleksi koji su vezani na kromosome. Premda su sile koje djeluju u diobenom vretenu iscrpno istraživane, i dalje je nepoznato kako su one uravnotežene. Poznato je da se između sestrinskog para kinetohora nalazi još jedna skupina mikrotubula, koju mi ovdje nazivamo premosni mikrotubuli. Razvili smo model koji uključuje kinetohorne i premosne mikrotubule, te sile i momente sila koji djeluju me.u njima. Mikrotubuli su u modelu opisani kao tanki elastični štapovi koji se svijaju i uvijaju pod djelovanjem sila i momenata sila na njihovim krajevima. Iz oblika snopova mikrotubula, pomoću modela možemo odrediti kolike sile i momenti sila djeluju unutar diobenog vretena. Usporedbom sa izmjerenim oblicima predvidjeli smo da je sila na kinetohori Fk ~ 300 pN, a u polu F0 ~ 30 pN. Pokazali smo da premosni mikrotubuli omogućuju koegzistenciju sile kompresije u blizini polova te sile tenzije u blizini kinetohora, što je već niz godina otvoreno pitanje. Pokazali smo da je diobeno vreteno kiralno, te da su za kiralni oblik snopova mikrotubula odgovorni momenti sila u sustavu dva sestrinska kinetohorna vlakna i premosnog vlakna. Zaključujemo da uz sile u diobenom postoje i momenti sila, koje generiraju molekularni motori, te da oni zajedno sa silama određuju njegovu arhitekturu.

Abstract (english)

At the onset of division, the cell forms a network of protein filaments, mitotic spindle, which divides genetic material between the two nascent daughter cells. It is known that protein filaments, microtubules, behave as elastic objects. Forces that govern the division are exerted by k-fibres, bundles of microtubules which end at the kinetochores, protein complexes which mechanically couple microtubules to the chromosomes. Although forces that exist in mitotic spindle have been studied thoroughly, how they are balanced still remains elusive. It is known that nonkinetochore microtubules exist between the sister pairs of kinetochores, which we term bridging microtubules. We have developed a model that includes k-fibres and bridging fibre, as well as forces and torques acting between them. We have modelled the microtubule bundles as slender elastic rods that undergo bending and torsion due to the forces and torques exerted at its ends. By using our model and known shape of microtubule bundles, we can infer the forces and torques that are present in mitotic spindle. We have compared shapes obtained from theory and experiment, and predicted that the force at kinetochore is Fk ~ 300 pN and the force at pole is F0 ~ 30 pN. By using a theoretical model that includes the bridging fibre, we explained the coexistence of the tension at kinetochores and compression at poles, which has been an open question for a few years now. In addition, we show that mitotic spindle is chiral, and that torques acting on the bridging and k- fibres spindle are responsible for chiral shapes of microtubule bundles. We conclude that, in addition to forces, torques that are generated by the motor proteins exist in the spindle and determine its architecture.

• Keywords: diobeno vreteno; metafaza; premosni mikrotubuli; teorija elastičnosti; statička Kirchoffova jednadžba; kiralnost
• Keywords (english): mitotic spindle; metaphase; bridging microtubules; elasticity theory; static Kirchoff equation; chirality
• Language: croatian
• URN:NBN: urn:nbn:hr:217:567368
• Study programme: Title: Physics; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje fizika (doktor/doktorica znanosti, područje prirodnih znanosti, polje fizika)
• Type of resource: Text
• Extent: 129 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-10-20 08:26:38