11 kinesiska forskare har genomfört studier kring morfogenes,dvs förändringsprocesser med olika tekniker och områden.De har gått igenom tidigare studier som anses vara "sanningar" och ligga till grund för synen hur celler agerar vid givna situationer.Resurser har ställts till deras förfogande och de har använt sig av ny teknik och ny kunskap för att se om principerna vid morfogenes förändrats i någon mån och då kanske har betydelse för nutida forskning och även behandling vid exempelvis cancersjukdom.Ett ambitiöst forskningsprojekt vill jag påstå.Man blir nyfiken på bevekelsegrunder och vidare motiv att sätta upp ett sådant maffigt projekt.Förmodligen vill landet Kina spänna musklerna och visa omvärlden vilken (enastående) forskarkompetens landet har.
Self-Organization of Tissue Growth by Interfacial Mechanical Interactions in Multilayered Systems
Abstract
Morphogenesis is a spatially and temporally regulated process involved in various physiological and pathological transformations. In addition to the associated biochemical factors, the physical regulation of morphogenesis has attracted increasing attention. However, the driving force of morphogenesis initiation remains elusive. Here, it is shown that during the growth of multilayered tissues, a morphogenetic process can be self-organized by the progression of compression gradient stemmed from the interfacial mechanical interactions between layers. In tissues with low fluidity, the compression gradient is progressively strengthened during growth and induces stratification by triggering symmetric-to-asymmetric cell division reorientation at the critical tissue size. In tissues with high fluidity, compression gradient is dynamic and induces cell rearrangement leading to 2D in-plane morphogenesis instead of 3D deformation. Morphogenesis can be tuned by manipulating tissue fluidity, cell adhesion forces, and mechanical properties to influence the progression of compression gradient during the development of cultured cell sheets and chicken embryos. Together, the dynamics of compression gradient arising from interfacial mechanical interaction provides a conserved mechanism underlying morphogenesis initiation and size control during tissue growth.
Introduction
Morphogenesis is a common process that occurs widely in embryonic development, tissue regeneration, and cancer progression. The orchestration of morphogenetic processes is complex, and involves spatial and temporal regulation by biochemical factors (e.g., cell polarity signals and morphogen gradient) and physical factors. Emerging studies have revealed that proper morphogenesis relies on the mechanical force of the cells and their environment. For example, apical constriction of cells caused by the contractility of myosin, cell rearrangement (e.g., cell intercalation), and tissue-stiffness-dependent cell migration has been reported as an important mechanisms in tissue shaping during embryonic development. These studies indicate the essential functions of cellular and molecular mechanics in the progression of morphogenesis. However, the upstream events, especially the initial driving forces of morphogenesis, remain unknown.
Most biological tissues have multilayered structures. The interactions between layers are essential in tissue homeostasis maintenance and morphogenesis during embryonic development and pathological progression. For example, the interaction between cancer cells and their adjacent stroma plays a key role in the progression of the diseases, including tumor invasion. In addition to biochemical communications, increasing evidence has shown the essential role of physical interactions between adjacent layers in the regulation of morphogenesis. For instance, follicle formation in chicken embryos is initiated by mechanical forces transduced from the dermal layer to the epidermal layer. The villi of human and chicken guts are formed by the compressive stresses generated by smooth muscle layers on the endoderm and mesenchyme layers. These studies reveal that morphogenesis processes are dependent on the mutual collaboration and mechanical compatibility of multiple layers. In this sense, it is necessary and important to address the general mechanism underlying the initiation of morphogenesis during the growth of various multilayered tissues.
Here, by combining biological experiments, theoretical analysis, and numerical simulations, we report a general mechanism underlying the initiation of morphogenesis driven by the progression of compression gradient stemmed from the interfacial mechanical interactions between growing tissue layers.
Naturligtvis kom de fram till ny kunskap,värdefull sådan som kommer ha "impact" för forskare och kommande studier där morfogenes ingår.Se mitt fetade avsnitt ovanför för att förstå satsningen Kina la på detta projekt.
Läs sen avsnitt 3 Discussion och se vad de föreslår för forskarkollektivet världen över.Alltså den förändrade synen på morfogenes "från - till".Små ord som för de flesta inte tyder på så stor förändring,men för de initierade förmodligen ganska omvälvande innebörd.
Forskarnas studier är som skräddarsytt för användning av PHI`s HoloMonitor är min syn.Nästan så man undrar om PHI bett forskarna genomföra dessa studier om morfogenes.(självklart är fallet inte så)
Referensangivelserna till HoloMonitor är flera :
Live Imaging
Live cell imaging was performed in a Leica microscope or HoloMonitor M4, enclosed in an incubator to maintain the samples at 37 °C and 5% of CO2 throughout the experiments. Images were acquired every 10 min with Leica software. Spindle-rocking experiments were acquired every 3 min with the Leica microscope. HoloMonitor M4 is a quantitative phase-imaging-based cell analyzer utilizing the principle of digital holographic microscopy. Live cell imaging was performed in HoloMonitor M4, enclosed in an incubator to maintain the samples at 37 °C and 5% of CO2 throughout the experiments. Images were acquired every 10 min with HStudio 2.7.
Image Processing, Segmentation, and Quantification
In cell data analysis of HoloMonitor M4, cell area, cell thickness, cell sheet area, and cell sheet thickness were analyzed by the software HStudio 2.7. HStudio 2.7 can automatically segment and extract physical parameters of the cell. For more details, please refer to the official manual.
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| f) The representative live images of a growing HeLa cell sheet using HoloMonitor M4 time-lapse cytometer. Scale bar: 150 µm. |
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| g) The representative images of dividing cells before (0 h) and after (75 h) critical compression during HeLa cell sheet growth using HoloMonitor M4 time-lapse cytometer. |
Scrolla sen ner till Supporting Information.Där hittar ni filmer tagna med HoloMonitor.
Avslutningsvis under Tack till ...hittas följande : This work was supported by the National Key R&D Program of China (2017YFA0506500, 2016YFC1102203, and 2016YFC1101100), the National Natural Science Foundation of China (31370018, 11972206, 11902114, U20A20390, 11827803, and 11902020), and Fundamental Research Funds for the Central Universities (ZG140S1971).
Et voilà
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