Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function
Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today's most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for actuation. These capabilities are widely used in clinical techniques such as diagnostic ultrasound, magnetic resonance imaging, focused ultrasound ablation, and magnetic particle hyperthermia. Each of these modalities offers spatial and temporal precision that could be used to study a multitude of cellular processes in vivo. However, connecting these techniques to cellular functions such as gene expression, proliferation, migration, and signaling requires the development of new biochemical tools that can interact with sound waves and magnetic fields as optogenetic tools interact with photons. Here, we discuss the exciting challenges this poses for biomolecular engineering and provide examples of recent advances pointing the way to greater depth in in vivo cell biology.
© 2017 American Chemical Society. Received: May 8, 2017; Revised: June 24, 2017; Published: August 7, 2017. Special Issue: Seeing Into Cells Related work in the Shapiro laboratory is also supported by the Heritage Medical Research Institute, the National Institutes of Health, the Defense Advanced Research Projects Agency, the Jacobs Institute for Molecular Engineering in Medicine, the Caltech Center for Environmental Microbial Interactions, the Human Frontiers Science Program, the Burroughs Wellcome Fund, the Pew Scholarship in the Biomedical Sciences, the Sontag Foundation, and the Packard Fellowship for Science and Engineering. D.M. is supported by the Human Frontiers Science Program Cross Disciplinary Postdoctoral Fellowship (Award No. LT000637/2016). A.F. is supported by the Natural Sciences and Engineering Research Council of Canada PGSD. We thank members of the Shapiro Laboratory for helpful discussions. The authors declare no competing financial interest.
Accepted Version - nihms-978819.pdf