5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Multi-scale cellular engineering: From molecules to organ-on-a-chip

      other

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches.

          Related collections

          Most cited references45

          • Record: found
          • Abstract: found
          • Article: not found

          The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder.

          A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

            Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices

              Sample multiplexing facilitates scRNA-seq by reducing costs and artifacts such as cell doublets. However, universal and scalable sample barcoding strategies have not been described. We therefore developed MULTI-seq: m ultiplexing u sing l ipid- t agged i ndices for single-cell and single-nucleus RNA sequencing. MULTI-seq reagents can barcode any cell type or nucleus from any species with an accessible plasma membrane. The method involves minimal sample processing, thereby preserving cell viability and endogenous gene expression patterns. MULTI-seq enables doublet identification, which improves data quality and increases cell throughput by minimizing the negative consequences of Poisson droplet loading. MULTI-seq sample classifications additionally identify cells with low RNA content that would otherwise be discarded by standard quality-control workflows. We use MULTI-seq to track the dynamics of T-cell activation, perform a 96-plex perturbation experiment with primary human mammary epithelial cells, and multiplex cryopreserved tumors and metastatic sites isolated from a patient-derived xenograft mouse model of triple-negative breast cancer.
                Bookmark

                Author and article information

                Contributors
                Journal
                APL Bioeng
                APL Bioeng
                ABPID9
                APL Bioengineering
                AIP Publishing LLC
                2473-2877
                March 2020
                03 March 2020
                03 March 2020
                : 4
                : 1
                : 010906
                Affiliations
                [1 ]Department of Cardiothoracic Surgery, Stanford University , Stanford, California 94305, USA
                [2 ]Stanford Cardiovascular Institute, Stanford University , Stanford, California 94305, USA
                [3 ]Department of Mechanical Engineering, Stanford University , Stanford, California 94305, USA
                [4 ]Department of Biomedical Engineering, Institute for Cell Engineering, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, USA
                [5 ]Department of Surgery, School of Medicine, University of California Davis , Sacramento, California 95817, USA
                [6 ]Department of Biomedical Engineering, University of California Davis , Davis, California 95616, USA
                [7 ]Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children , Sacramento, California 95817, USA
                [8 ]Department of Bioengineering, Jacob School of Engineering, University of California San Diego , La Jolla, California 92093, USA
                [9 ]Department of Bioengineering, University of California Berkeley , Berkeley, California 94720, USA
                [10 ]Department of Chemical and Biomolecular Engineering, University of California Berkeley , Berkeley, California 94720, USA
                [11 ]Department of Bioengineering, University of California , Los Angeles, California 90095, USA
                [12 ]Department of Radiological Sciences, University of California , Los Angeles, California 90095, USA
                [13 ]California Nanosystems Institute, University of California , Los Angeles, California 90095, USA
                Author notes
                [a) ] Authors to whom correspondence should be addressed: ngantina@ 123456stanford.edu . Tel.: (650) 849-0559. Fax: (650) 725-3846 and song_li@ 123456ucla.edu . Tel.: 310-206-5260.
                Author information
                https://orcid.org/0000-0003-2298-6790
                https://orcid.org/0000-0002-9287-3401
                https://orcid.org/0000-0003-3652-2540
                https://orcid.org/0000-0002-2985-3627
                https://orcid.org/0000-0003-1642-5380
                https://orcid.org/0000-0003-0265-326X
                https://orcid.org/0000-0002-9996-4883
                https://orcid.org/0000-0002-2692-1524
                https://orcid.org/0000-0002-4760-8828
                Article
                1.5129788 APB19-RV-00110
                10.1063/1.5129788
                7054123
                4dd9a160-7633-46a7-afbb-f6efa2dfed02
                © Author(s).

                2473-2877/2020/4(1)/010906/10

                All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 October 2019
                : 28 January 2020
                Page count
                Pages: 10
                Funding
                Funded by: National Science Foundation https://doi.org/10.13039/100000001
                Award ID: 18346550
                Categories
                Perspectives
                Custom metadata

                Comments

                Comment on this article