Biology subjects

Petzold, H.

Publications and source records attributed to Petzold, H..

4 recordsLinked to original sources

bioRxiv2024

Control of lumen geometry and topology by cell proliferation rate and pressure

Many internal organs in multicellular organisms comprise epithelia which enclose fluid-filled cavities. These are referred to as lumens and their formation is regulated by a wide range of processes, including epithelial polarization, secretion, exocytosis and actomyosin contractility [1, 2]. While these mechanisms have shed light on lumen growth, what controls lumen morphology remains enigmatic. Here we use pancreas organoids to explore how lumens acquire either a spherical shape or a branched topology [3]. Combining computational simulations based on a phase field model with experimental measurements we reveal that lumen morphology arises from the balance between the cell cycle duration and lumen pressure, with more complex lumen at low pressure and fast proliferation rates. Moreover, the manipulation of proliferation and lumen pressure in silico and in vitro is sufficient to alter and reverse the morphological trajectories of the lumens. Increasing epithelial permeability of spherical lumens lead to lower lumen pressure and converts their morphology to complex lumen shapes, highlighting its crucial role. In summary, the study underscores the importance of balancing cell proliferation, lumen pressure, and epithelial permeability in determining lumen morphology, providing insights relevant to other organs, for tissue engineering and cystic disease understanding and treatment [4].

developmental biology↗

bioRxiv2024

Generic rules of lumen nucleation and fusion in epithelial organoids

Many internal organs in the body harbor a fluid-filled lumen. The mechanisms of lumens initiation and fusion have been reported as dependent on organ-type during organogenesis. In contrast, the physics of lumen suggests that force balance between luminal pressure and cell mechanics could lead to conserved rules which may unify their self-organisation. However, this hypothesis lacks experimental evidence. Here we compare lumen dynamics for three different systems (MDCK cysts, pancreatic spheres, and epiblast cysts) by using quantitative cell biology, microfabrication and theory. We report that initial cell number determines the maximum number of lumens but does not impact the steady state which is a final single lumen. In addition, lumen numbers exhibit two phases over time, a nucleation phase followed by a fusion phase. In the nucleation phase, lumens form between two cells in pancreatic and MDCK cysts whereas they form at the rosette stage between ten cells in epiblasts. In the second phase, lumens fuse by an increase in lumen volume for pancreatic spheres and MDCK cysts, whereas cell convergent directional motion leads to lumens fusion in epiblasts. We show that these phenomena are associated to the luminal hydrostatic pressure. We support these results with theoretical arguments and numerical simulations. We finally use MDCK cysts to manipulate cell adhesion and lumen volume and we successfully reproduce the fusion dynamics of pancreatic spheres and epiblasts. Our results reveal self-organisation rules of lumens across systems with relevance for morphogenesis during development and for the design of synthetic organs.

biophysics↗

bioRxiv2019

Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice

Rod photoreceptors of nocturnal mammals display a striking inversion of nuclear architecture, which has been proposed as an evolutionary adaptation to dark environments. However, the nature of visual benefits and underlying mechanisms remains unclear. It is widely assumed that improvements in nocturnal vision would depend on maximization of photon capture, at the expense of image detail. Here we show that retinal optical quality improves 2-fold during terminal development, which, confirmed by a mouse model, happens due to nuclear inversion. We further reveal that improved retinal contrast-transmission, rather than photon-budget or resolution, leads to enhanced contrast sensitivity under low light condition. Our findings therefore add functional significance to a prominent exception of nuclear organization and establish retinal contrast-transmission as a decisive determinant of mammalian visual perception. One Sentence SummaryOur study reveals that chromatin compaction in rod cells augments contrast sensitivity in mice.

biophysics↗

bioRxiv2018

Active gelation breaks time-reversal-symmetry of mitotic chromosome mechanics

In cell division, mitosis is the phase in which duplicated sets of chromosomes are mechanically aligned to form the metaphase plate before being segregated in two daughter cells. Irreversibility is a hallmark of this process, despite the fundamental laws of Newtonian mechanics being time symmetric.\n\nHere we show experimentally that mitotic chromosomes receive the arrow of time by time-reversal-symmetry breaking of the underlying mechanics in prometaphase. By optically inducing hydrodynamic flows within prophase nuclei, we find that duplicated chromatid pairs initially form a fluid suspension in the nucleoplasm: although showing little motion on their own, condensed chromosomes are free to move through the nucleus in a time-reversible manner. Actively probing chromosome mobility further in time, we find that this viscous suspension of chromatin transitions into a gel after nuclear breakdown. This gel state, in which chromosomes cannot be moved by flows, persists even when chromosomes start moving to form the metaphase plate. Complemented by minimal reconstitution experiments, our active intra-nuclear micro-rheology reveals time-reversal-symmetry breaking of chromosome mechanics to be caused by the transition from a purely fluid suspension into an active gel.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC=\"FIGDIR/small/296566_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@15b00edorg.highwire.dtl.DTLVardef@199eb2dorg.highwire.dtl.DTLVardef@1f0550org.highwire.dtl.DTLVardef@95cb5a_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryFlows induced in living cell nuclei reveal the rheological changes that bring chromosomes under mechanical control during mitosis.

biophysics↗