Optical plasticity of mammalian cells. Issue 4 (7th January 2021) - Subramanian, Kaushikaram
Abstract: Transparency is widespread in nature, ranging from transparent insect wings to ocular tissues that enable you to read this text, and transparent marine vertebrates. And yet, cells and tissue models in biology are usually strongly light scattering and optically opaque, precluding deep optical microscopy. Here we describe the directed evolution of cultured mammalian cells toward increased transparency. We find that mutations greatly diversify the optical phenotype of Chinese Hamster Ovary cells, a cultured mammalian cell line. Furthermore, only three rounds of high‐throughput optical selection and competitive growth are required to yield fit cells with greatly improved transparency. Based on 15 monoclonal cell lines derived from this directed evolution experiment, we find that the evolved transparency frequently goes along with a reduction of nuclear granularity and physiological shifts in gene expression profiles. In the future this optical plasticity of mammalian cells may facilitate genetic clearance of living tissues for in vivo microscopy. Abstract : Biological cells are highly light‐scattering, largely precluding the optical access of light microscopes into living tissues. Using a scheme of mutation and high‐throughput optical selection, the authors present the directed evolution of mammalian cells towards increased transparency. The evolved cells replicate and reflect a physiological state, while showing strongly reduced light‐scattering, which motivates the authors to propose the generation of genetically enhanced, optically superior tissues (GHOSTs) to advance life microscopy.