Novel nanoscale fiber-optic stress sensors: for mechanical probing at the molecular and cellular levels

Underlying most biological processes are unique nanobiomechanical events that help drive reactions and guide chemical pathways. These small force cues can be subtle and difficult to follow, but they are a complex part of environmental response and life support. With the continuous development of ultrasensitive nanostress instruments, observing, measuring and manipulating these force processes in vitro and even in vivo has been an ongoing goal to gain a more complete understanding of biomechanical phenomena.

Underlying most biological processes are unique nanobiomechanical events that help drive reactions and guide chemical pathways. These small force cues can be subtle and difficult to follow, but they are a complex part of environmental response and life support. With the continuous development of ultrasensitive nanostress instruments, observing, measuring and manipulating these force processes in vitro and even in vivo has been an ongoing goal to gain a more complete understanding of biomechanical phenomena.

Novel nanoscale fiber-optic stress sensors: for mechanical probing at the molecular and cellular levels

Figure 1 Overview of the NOFT system. a, Hooke’s law can be used to model the response of the NOFT platform. The spring constant of the polymer cladding as well as the scattering intensity of the NPs increase with the compression of the film. b, Overall workflow for fabricating NOFT devices: SnO2 waveguide synthesis; generation of compressible polymer grafts; attachment of gold nanoparticles; far-field imaging, data acquisition and analysis

Currently, it is possible to obtain real-time information from individual molecules to larger cellular structures and tissues. However, scaling down the size of nanomechanical sensors remains challenging due to force feedback mechanisms and active components. Having a compact force sensor enables many measurements, including intracellular monitoring, minimally invasive detection, and high-resolution detection. Ideally, the sensor is small enough to minimize the inflammatory response, with high resolution and the ability to track multiple mechanical events simultaneously. Equally important as size is the ability to operate in different modes and detect various types of nanoforce features. For example, in a direct contact mode, the sensor would be able to sense tiny forces acting on it, however, it would also be advantageous to have a non-contact mode where the sensor detects signals such as sound waves originating from volume changes or moving masses. To do this, the sensor must be designed to interact with the sound waves and produce a detectable signal above the noise level. The realization of these new ultrasensitive force sensors requires new methods and innovative engineering. There is a current need to develop ultrasensitive nanomechanical instruments with high spatial and force resolution and capable of operating in various biological environments.

Figure 2. NOFT operation for detection of nanomechanical signals. a, General schematic of the NOFT system when set up to detect mechanical or acoustic features. Data processing of the acoustic signals includes Fourier transform (FT) of the collected scattered signals. b, The ratio of the scattered signal over the mean signal (coefficient of variance) to the mean scattered signal of NOTF devices with or without bacteria. c, FT of light scattering signals from NOFT devices in the presence and absence of cardiomyocytes

Scientists at the University of California, San Diego have proposed a compact nanofiber optical stress sensor (NOFT) with sub-picoNewtonian force sensitivity and nanoscale scale, paving the way for exploring complex mechanical phenomena within biomolecular systems. The NOFT platform consists of SnO2 nanofiber fibers equipped with thin, compressible polymer cladding filled with plasmonic nanoparticles (NPs). This combination allows to quantify the angstrom-scale motion of NPs by tracking the optical scattering as they interact with the near-field of the fiber. Once the mechanical properties of the compressible cladding are fully characterized, the distance-dependent optical signal can be converted into force. In this protocol, the details of the synthesis, characterization and calibration of the NOFT system are described. The overall protocol from synthesis of nanofiber optics to acquisition of nanostress data required 72 hours. The related content is titled “Nanoscale fiber-optic force sensors for mechanical probing at themolecular and cellular level”, published in the journal “Nature Protocols”.

Figure 3 Near-field scattering and attachment of gold nanoparticles. a, Experimental data showing the normalized scattering intensity of individual gold nanoparticles separated from WG-NPs using self-assembled polyelectrolyte layers. b, Top: Schematic illustration of attached NP reference and transmission electron microscopy (TEM) images after deposition on SnO2 nanofibers.Bottom: Schematic illustration of NP sensor attachment and TEM image after deposition on SnO2 nanofibers

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