Organ size control via hydraulically gated oscillations

Abstract

Hollow vesicular tissues of various sizes and shapes arise in biological organs such as ears, guts, hearts, brains and even entire organisms. Regulating their size and shape is crucial for their function. Although chemical signaling has been thought to play a role in the regulation of cellular processes that feed into larger scales, it is increasingly recognized that mechanical forces are involved in the modulation of size and shape at larger length scales. Motivated by a variety of examples of tissue cyst formation and size control that show simultaneous growth and size oscillations, we create a minimal theoretical framework for the growth and dynamics of a soft, fluid-permeable, spherical shell. We show that these shells can relieve internal pressure by bursting intermittently, shrinking and re-growing, providing a simple mechanism by which hydraulically gated oscillations can regulate size. To test our theory, we develop an experimental set-up to monitor the growth and oscillations of a hollow tissue spheroid growing freely or when confined. A simple generalization of our theory to account for irreversible deformations allows us to explain the time scales and the amplitudes of oscillations in terms of the geometry and mechanical properties of the tissue shells. Taken together, our theory and experimental observations show how soft hydraulics can regulate the size of growing tissue shells.

Physical basis of lumen shape and stability in a simple epithelium

“…The advantages of pressure-independent lumen growth remain to be firmly established in an in vivo context. However, we note that this mechanism is predicted to be physically robust and energy efficient relative to pressure-driven growth, which exposes tissues to pressuredriven rupture (Chan et al, 2019;Ruiz-Herrero et al, 2017). Notably, cells in some model systems continue to utilize pressure-independent mechanisms to grow lumens beyond these intermediate stages, for example, by addition of cells or by fusion of smaller lumens (Cerruti et al, 2013;Dumortier et al, 2019).…”

“…Previous work in MDCK spheroids and other systems has assumed that lumen growth is driven by hydrostatic pressure (Fig. 1a) (Chan et al, 2019;Dasgupta et al, 2018;Latorre et al, 2018;Ruiz-Herrero et al, 2017). In this model, lumen growth is governed by the Young-Laplace equation, which states that the pressure difference (P) between the cells and the lumen is counterbalanced by the surface tension (ɣ) of the lumen surface (apical faces of the cells) and inversely proportional to the lumen radius (r): !"…”

“…= $% & . The presence of a pressure gradient is motivated by work that showed that ion channels are critical for lumen formation and expansion in vitro and in vivo (Bagnat et al, 2007;Yap et al, 1993), and by pressure-driven fluctuations in lumen size in some model systems (Chan et al, 2019;Ruiz-Herrero et al, 2017). Importantly, this model predicts that lumen shape must be close to spherical.…”

Theory of mechano-chemical patterning in biphasic biological tissues

“…Systems such as digits patterning, where cell volume fraction spatial pattern appears concomitant to morphogen patterns [26], or planarian antero-posterior patterning, where pairs of activator/inhibitor have not been clearly identified [41], provide possible testing grounds for our model. Interestingly, large-scale extracellular fluid flows have been increasingly observed during embryo development, not only in the classical case of cilia driven flows [48], but also due to mechanical forces arising from cellular contractions as well as osmotic and poro-viscous effects [49,50], calling for a more systematic understanding of passive vs. active transport mechanisms during embryonic pattern formation. Whether biological examples of Turing patterning instabilities, such as left-right or dorso-ventral patterning, digits pattern formation or skin appendages patterns are causally associated with concomitant changes in cell volume and/or cell packing remains a result to be experimentally investigated.…”

Morphogenesis one century afterOn Growth and Form

“…The mechanics of developmental processes involves multiple scales, and a number of papers discuss examples of this: Boselli and colleagues consider the role of fluid flows and shear stress in orienting tissue movements (Boselli et al, 2017), Nelson and colleagues look at the effects of pressure on early branching processes (Nelson et al, 2017), Ruiz-Herrero and colleagues provide a general framework for size control of growing tissue cysts (Ruiz-Herrero et al, 2017), Lefevre and colleagues analyse multiscale branching in the mammalian kidney (Lefevre et al, 2017), and axis elongation in the avian embryo is the focus of the work of Bénazéraf and colleagues (Bénazéraf et al, 2017).…”