Physical models of epithelial morphogenesis

doctoral thesis

Jan Rozman (Author), Primož Ziherl (Mentor)

Abstract

The Thesis addresses selected theoretical problems of the mechanics of biological systems that involve epithelial tissues. We first develop a vertex model of epithelial shells that resemble small organoids. We find that collective effects in a system of cell with identical mechanical properties are sufficient for the formation of spherical, stomatocyte, and budded morphologies. However, the formation of branched model organoids also requires a high degree of junctional activity, possibly because it enables a temporary aggregation of topological defects. To elucidate our numerical results, we develop an effective elasticity theory, which allows one to estimate the apico-basal polarity from the tissue-scale modulation of cell height. We then compare these results to morphologies that emerge in a more general model tissue: A strained unsupported epithelial monolayers subject to active junctional noise due to stochastic binding and unbinding of myosin. We find that while uniaxial, biaxial, and isotropic in-plane compressive strains do lead to the formation of longitudinal, herringbone pattern, and labyrinthine folds, respectively, the villi morphology again appears only if junctional tension fluctuations are strong enough to fluidize the tissue. Moreover, the fluidized epithelium features villi even in absence of compressive strain. We also analyze several details of the different epithelial forms including the role of strain rate and the modulation of tissue thickness across folds. Lastly, we use a discrete model that takes into account the topology of linked cells, but not their geometry, to study the emergence of clonal dominance. This phenomenon refers to the situation where the descendants (also known as clones) of one or a few founder cells contribute disproportionally to the cell population of the final tissue. While this is often explained by pre-existing advantages in, e.g., bacterial colonies, it is less understood in development where such biases should not be present. Using clone size data from the fruit fly egg chamber epithelium, we show that clonal dominance can emerge spontaneously due to the coupling of cell divisions.

Keywords

biological systems;epithelial tissues;morphogenesis;vertex model;surface tension;organoids;villi;fruit fly;egg chamber;clonal dominance;

Data

Language:	English
Year of publishing:	2022
Typology:	2.08 - Doctoral Dissertation
Organization:	UL FMF - Faculty of Mathematics and Physics
Publisher:	[J. Rozman]
UDC:	577.35(043.3)
COBISS:	110555139
Views:	93
Downloads:	30
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary title:	Fizikalni modeli epitelijske morfogeneze
Secondary abstract:	Delo obravnava izbrana teoretična vprašanja s področja mehanike bioloških sistemov, ki vključujejo epitelijska tkiva. Najprej razvijemo ogliščni model epitelijskih lupin, ki spominjajo na majhne organoide. Ugotovimo, da kolektivni pojavi v sistemu celic z enakimi mehaničnimi lastnostmi zadoščajo za tvorbo okroglih, stomatocitnih in brstečih morfologij, za tvorbo razvejenih modelskih organoidov pa je potrebna tudi visoka stopnja stične aktivnosti, morda zato, ker omogoča začasno agregacijo topoloških defektov. Za interpretacijo numeričnih rezultatov razvijemo teorijo elastičnosti, ki omogoča oceno apikobazalne polarnosti iz modulacije višine celice. Nato primerjamo te rezultate z morfologijami, ki se pojavijo v bolj generičnem modelskem tkivu, in sicer v nepodprtem epitelijskem monosloju, podvrženem aktivnemu šumu na medceličnih stikih zaradi stohastične vezave in sproščanja miozina. Medtem ko vodijo enoosni, dvoosni in izotropni stisk do tvorbe longitudinalnih, cikcakastih oziroma labirintnih gub, se resice pojavijo le, če je aktivnost na stikih dovolj močna, da fluidizira tkivo. Izkaže se celo, da za nastanek resic v fluidiziranem epiteliju stisk sploh ni potreben. Analiziramo tudi več podrobnosti različnih epitelijskih oblik vključno z vlogo hitrosti deformacije in modulacijo debeline tkiva po gubah. Nazadnje se lotimo preučevanja nastanka dominantnih klonov, in sicer v diskretnem modelu, ki upošteva topologijo povezanih celic, ne pa tudi njihove geometrije. O dominantnih klonih govorimo, ko je potomcev (oz. klonov) majhnega deleža začetnih celic v končnem tkivu nesorazmerno mnogo. V kolonijah bakterij je nastanek dominantnih klonov npr.~mogoče pripisati genetskim ali pozicijskim prednostim dela populacije. Slabše pa ta fenomen razumemo v razvoju, kjer takih prednosti ni pričakovati. Na osnovi podatkov o velikosti klonov v jajčni kamrici vinske mušice pokažemo, da lahko dominantni kloni nastanejo spontano kot posledica sklopitve celičnih delitev.
Secondary keywords:	biološki sistemi;epitelijska tkiva;morfogeneza;ogliščni model;površinska napetost;organoidi;resice;vinska mušica;jajčna kamrica;dominantni kloni;Biološki sistemi;Disertacije;Mehanika;
Type (COBISS):	Doctoral dissertation
Study programme:	0
Embargo end date (OpenAIRE):	1970-01-01
Thesis comment:	Univ. v Ljubljani, Fak. za matematiko in fiziko, Oddelek za fiziko
Pages:	163 str.
ID:	15532656