With the model we can simulate the effect of biophysical aspects that affect duct formation. Here, we built a computational model of biliary lumen formation which represents every cell and its function in detail. However, how these mechanisms are orchestrated in time and space is difficult to understand. The initial step in bile duct development is the formation of a biliary lumen, a process which involves several cellular mechanisms, such as cell division and polarization, and secretion of fluid. Our simulations suggest that successful bile duct lumen formation requires a simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size. This model permits realistic simulations of tissue and cell mechanics at sub-cellular scale. Here, guided by the quantification of morphological features and expression of genes in bile ducts from embryonic mouse liver, we sharpened these hypotheses and collected data to develop a high resolution individual cell-based computational model that enables to test alternative hypotheses in silico. Several hypotheses have been proposed to characterize the biophysical mechanisms driving initial bile duct lumen formation during embryogenesis. A deep understanding of the processes underlying bile duct lumen formation is crucial to identify intervention points to avoid or treat the appearance of defective bile ducts. Disruptions in this process caused by defective embryonic development, or through ductal reaction in liver disease have a major impact on life quality and survival of patients. OpenStax CNX.Biliary ducts collect bile from liver lobules, the smallest functional and anatomical units of liver, and carry it to the gallbladder. Text adapted from: OpenStax, Concepts of Biology.
Unless otherwise noted, images on this page are licensed under CC-BY 4.0 by OpenStax. (credit: modification of work by Magnus Manske) References Figure 1 The endomembrane system works to modify, package, and transport lipids and proteins. The SER’s functions include synthesis of carbohydrates, lipids (including phospholipids), and steroid hormones detoxification of medications and poisons alcohol metabolism and storage of calcium ions. The smooth endoplasmic reticulum (SER) is continuous with the RER but has few or no ribosomes on its cytoplasmic surface (see Figure 1). Since the RER is engaged in modifying proteins that will be secreted from the cell, it is abundant in cells that secrete proteins, such as the liver. If the phospholipids or modified proteins are not destined to stay in the RER, they will be packaged within vesicles and transported from the RER by budding from the membrane ( Figure 1).
The RER also makes phospholipids for cell membranes. The rough endoplasmic reticulum (RER) is so named because the ribosomes attached to its cytoplasmic surface give it a studded appearance when viewed through an electron microscope. The ribosomes synthesize proteins while attached to the ER, resulting in transfer of their newly synthesized proteins into the lumen of the RER where they undergo modifications such as folding or addition of sugars. The membrane of the ER, which is a phospholipid bilayer embedded with proteins, is continuous with the nuclear envelope. There is a hollow portion inside ER tubules that is called the lumen.
However, these two functions are performed in separate areas of the endoplasmic reticulum: the rough endoplasmic reticulum and the smooth endoplasmic reticulum, respectively.
#Osmosis in er lumen series#
The endoplasmic reticulum (ER) (see Figure 1) is a series of interconnected membranous tubules that collectively modify proteins and synthesize lipids.
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