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Abstract The cell membrane is not only a physical barrier, but also a functional organelle that regulates the communication between a cell and its environment. The ability to functionalize the cell membrane with synthetic molecules or nanostructures would advance cellular functions beyond what evolution has provided. The aim of this Minireview is to introduce recent progress in using synthetic DNA and DNA‐based nanostructures for cell‐surface engineering. We first introduce chemical conjugation and physical binding methods for monovalent and polyvalent surface engineering. We then introduce the application of these methods for either the promotion or inhibition of cell–environment communication in numerous applications, including the promotion of cell–cell recognition, regulation of intracellular pathways, protection of therapeutic cells, and sensing of the intracellular and extracellular microenvironments. Lastly, we summarize current challenges existing in this area and potential solutions to solve these challenges.
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Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules’ diffusion. We show that signal inactivation sharpens signals, reducing variability in the arrival time at the nuclear membrane. Inactivation can also compensate for an observed slowdown in signal propagation induced by the presence of organelle barriers, leading to arrival times at the nuclear membrane that are comparable to models in which the cytosol is treated as an open, empty region. In the limit of strong signal inactivation this is achieved by filtering out molecules that traverse non-geodesic paths.
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- Award ID(s):
- 1902854
- PAR ID:
- 10336264
- Editor(s):
- Faeder, James R.
- Date Published:
- Journal Name:
- PLOS Computational Biology
- Volume:
- 16
- Issue:
- 11
- ISSN:
- 1553-7358
- Page Range / eLocation ID:
- e1008356
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The cell membrane is not only a physical barrier, but also a functional organelle that regulates the communication between a cell and its environment. The ability to functionalize the cell membrane with synthetic molecules or nanostructures would advance cellular functions beyond what evolution has provided. The aim of this Minireview is to introduce recent progress in using synthetic DNA and DNA‐based nanostructures for cell‐surface engineering. We first introduce chemical conjugation and physical binding methods for monovalent and polyvalent surface engineering. We then introduce the application of these methods for either the promotion or inhibition of cell–environment communication in numerous applications, including the promotion of cell–cell recognition, regulation of intracellular pathways, protection of therapeutic cells, and sensing of the intracellular and extracellular microenvironments. Lastly, we summarize current challenges existing in this area and potential solutions to solve these challenges.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pcbi.1008356
