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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Developmental biology - Physics of Embryology

Careful - You Are Made of Glass

Tissues and organs are sculpted by 'jamming' during embryogenesis...

Ever wondered how groups of cells managed to build your tissues and organs while you were just an embryo?

Using techniques he developed, Otger Campās PhD of the University of California at Santa Barbara, along with his group, cracked a longstanding mystery of how embryos are constructed. Bringing a century-old hypothesis into the modern era, his techniques provide a foundation for studying other questions in human health, such as how cancers form and spread, and how to engineer organs.

"In a nutshell, we discovered a fundamental physical mechanism that cells use to mold embryonic tissues into their functional 3D shapes," explains Campās, a professor of mechanical engineering in UCSB's College of Engineering. Campās holds the Duncan & Suzanne Mellichamp Chair in Systems Biology. His group investigates how living systems self organize to build the remarkable structures and shapes found in nature.
Cells coordinate by exchanging biochemical signals, but they also hold onto and push each other to build body structures such as eyes, lungs and heart. It turns out sculpting the embryo is not far from glass molding or 3D printing. In their newest paper published in the journal Nature, Campās and colleagues reveal that cell groups switch from fluid to solid states when building the vertebrate embryo, in a way similar to how glass is heated, melted and molded into objects.

Most objects begin as fluids. From metallic structures to gelatin desserts, shape is made by pouring molten material into molds and cooling it into a solid object. As with a Chihuly glass sculpture, where carefully melted glass is slowly reshaped, cell regions of an embryo are triggered to 'melt' cell walls, changing cell content into a fluid state. From this "foamy" disorganization a new structure forms and as cells 'cool down' they settle into a tissue state.
"The transition from a fluid to a solid tissue state that we observed - is known in physics as 'jamming'. Jamming transitions are a very general phenomena that happens when particles in disordered systems, such as foams, emulsions or glasses, are forced together or cooled down."

Otger Campās; California NanoSystems Institute; Department of Molecular Cell; Developmental Biology; and Center for Bioengineering, University of California, Santa Barbara, CA, USA.

"We were able to measure physical quantities that couldn't be measured before, by inserting miniaturized probes into tiny developing embryos," said postdoctoral fellow Alessandro Mongera, lead author of the paper.
"One of the hallmarks of cancer is the transition between two different tissue architectures. This transition can, in principle, be explained as an anomalous switch from a solid-like to a fluid-like tissue state," Mongera points out. "The present study can help explain the mechanisms underlying this switch and highlight some of the potential druggable targets that hinder it."

Zebrafish, like other vertebrates, start off from a largely shapeless bunch of cells and need to transform into an elongated shape, with a head at one end and tail at the other. The physical reorganization of cells behind this process has always been something of a mystery. Surprisingly, the researchers found cells being made into tissue became physically like foam (as in the froth on a glass of beer) that 'freezes' into the architectural shape of that tissue.

These observations confirm the remarkable intuition of Victorian-era Scottish mathematician D'Arcy Thompson, 100 years ago in his seminal work "On Growth and Form." Thompson was interested in the effects of scale on the shape of animals and plants as well as the effects of surface tension on shaping soap films and cells.

"He was convinced that some of the physical mechanisms that give shapes to inert materials were also at play shaping living organisms. Remarkably, he compared groups of cells to foams and even the shaping of cells and tissues to glassblowing," says Campās. A century ago, there were no instruments that could directly test Thompson's ideas, though his work continues to be cited to this day.

The Nature paper is a jumping-off point for Campās researchers to begin investigating other processes related to embryonic development, such as how tumors physically invade surrounding tissues and how to engineer organs into specific 3D shapes.

Just as in clay moulding or glass blowing, physically sculpting biological structures requires the constituent material to locally flow like a fluid while maintaining overall mechanical integrity like a solid. Disordered soft materials, such as foams, emulsions and colloidal suspensions, switch from fluid-like to solid-like behaviours at a jamming transition1,2,3,4. Similarly, cell collectives have been shown to display glassy dynamics in 2D and 3D5,6 and jamming in cultured epithelial monolayers7,8, behaviours recently predicted theoretically9,10,11 and proposed to influence asthma pathobiology8 and tumour progression12. However, little is known about whether these seemingly universal behaviours occur in vivo13 and, specifically, whether they play any functional part during embryonic morphogenesis. Here, by combining direct in vivo measurements of tissue mechanics with analysis of cellular dynamics, we show that during vertebrate body axis elongation, posterior tissues undergo a jamming transition from a fluid-like behaviour at the extending end, the mesodermal progenitor zone, to a solid-like behaviour in the presomitic mesoderm. We uncover an anteroposterior, N-cadherin-dependent gradient in yield stress that provides increasing mechanical integrity to the presomitic mesoderm, consistent with the tissue transiting from a wetter to a dryer foam-like architecture. Our results show that cell-scale stresses fluctuate rapidly (within about 1 min), enabling cell rearrangements and effectively ‘melting’ the tissue at the growing end. Persistent (more than 0.5 h) stresses at supracellular scales, rather than cell-scale stresses, guide morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension is sustained by the reported rigidification of the presomitic mesoderm, which mechanically supports posterior, fluid-like tissues during remodelling before their maturation. The spatiotemporal control of fluid-like and solid-like tissue states may represent a generic physical mechanism of embryonic morphogenesis.

Alessandro Mongera, Payam Rowghanian, Hannah J. Gustafson, Elijah Shelton, David A. Kealhofer, Emmet K. Carn, Friedhelm Serwane, Adam A. Lucio, James Giammona and Otger Campās.

We thank E. Sletten for sharing custom-made fluorinated dyes. We also thank all laboratory members and the UCSB Animal Research Center for support. P.R. thanks B. Aigouy for assistance with Tissue Analyzer. A.M. thanks EMBO (EMBO ALTF 509-2013), Errett Fisher Foundation and Otis Williams Fund for financial support. This work was partially supported by the National Science Foundation (CMMI-1562910) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R21HD084285; R01HD095797).

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Sep 14, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

Bubbles in a foam of soapy water obey Plateau's laws. At every vertex the angle
is close to 109.47 degrees, the tetrahedral angle. Photo: Wikipedia.

Phospholid by Wikipedia