Abstract
Shear wave elastography (SWE) has been widely adopted for clinical in vivo imaging of tissue elasticity for disease diagnosis, and this modality can be a valuable tool for in vitro mechanobiology studies but its full potential has yet to be explored. Here we present a laser speckle contrast SWE system for noncontact monitoring the spatiotemporal changes of the extracellular matrix (ECM) stiffness in three-dimensional cancer cell culture system while providing submillimeter spatial resolution and temporal resolution of 10 s. The shear modulus measured was found to be strongly correlated with the ECM fiber density in two types of cell culture system (r = 0.832 with P < 0.001, and r = 0.642 with P = 0.024 for cell culture systems containing 4 mg/ml Matrigel with 1 mg/ml and 2 mg/ml collagen type I hydrogel, respectively). Cell migration along the stiffness gradient in the cell culture system and an association between cell proliferation and the local ECM stiffness was observed. As the elasticity measurement is performed without the need of exogenous probes, the proposed method can be used to study how the microenvironmental stiffness interacts with cancer cell behaviors without possible adverse effects of the exogenous particles, and could potentially be an effective screening tool when developing new treatment strategies.
Highlights
Information) or subsurface measurements with spatial information about the stiffness distribution in the submillimeter region
The spatial and temporal dynamics of the extracellular matrix (ECM) stiffness resulting from the interactions between the cells and ECM were unknown since the measurement technique requires direct contact, and the stress applied during bulk viscoelasticity measurements may resulted in the destruction of the culture sample
The imaging depth of particle-tracking microrheology is limited by the objective lens used to image the fluorescent particles, whereas atomic force microscopy is limited to surface viscoelasticity measurements
Summary
Information) or subsurface measurements with spatial information about the stiffness distribution in the submillimeter region. Particle-tracking microrheology[21,22] and atomic force microscopy[23,24,25] are minimally invasive techniques that have recently been implemented for viscoelastic measurements of 3D cell culture systems with high spatial resolutions (on the micrometer and submicrometer scales, respectively). Atomic force microscopy does not require the usage of fluorescent particles It employs a cantilever, which is modeled as an elastic beam with a known elasticity, to indent the sample and the measured deflection of the cantilever is used to estimate the viscoelasticity of the sample. The high motion sensitivity of laser speckle contrast shear wave elasticity imaging is hypothesized to be a suitable technique for performing elasticity measurements of samples with low scattering properties, such as a 3D cell culture system, with submillimeter spatial resolution and a temporal resolution of 10 s (a shear wave image can be acquired in less than 10 s)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
