Hemodynamic forces can be accurately measuredin vivowith optical tweezers

Abstract

Force sensing and generation at the tissular and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo. Optical trapping allows non-invasive probing of pico-Newton forces and thus emerged as a promising mean for assessing biomechanics in vivo. Nevertheless, the main obstacles rely in the accurate determination of the trap stiffness in heterogeneous living organisms, at any position where the trap is used. A proper calibration of the trap stiffness is thus required for performing accurate and reliable force measurements in vivo. Here, we introduce a method that overcomes these difficulties by accurately measuring hemodynamic profiles in order to calibrate the trap stiffness. Doing so, and using numerical methods to assess the accuracy of the experimental data, we measured flow profiles and drag forces imposed to trapped red blood cells of living zebrafish embryos. Using treatments enabling blood flow tuning, we demonstrated that such method is powerful in measuring hemodynamic forces in vivo with accuracy and confidence. Altogether, this study demonstrates the power of optical tweezing in measuring low range hemodynamic forces in vivo and offers an unprecedented tool in both cell and developmental biology.

Spectrum Degradation of Hippocampal LFP During Euthanasia

“…This jostling can be identified in the velocity profile as being a repeatable, low amplitude-high frequency event coupled to the macroscale heartbeat frequency. Finally, decomposing the red blood cell velocity would reveal a power spectra density eerily similar to the hippocampus, complete with a fundamental frequency, harmonics and a 1/f background (see figure 2B of Harlepp et al, 2017). In fact, one may suspect that the influence of pentobarbital on the power spectra of red blood cell velocity would parallel the degradation observed in the LFP, with the highest frequencies succumbing first.…”

Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

“…Such a hypothesis is exciting and further work is needed to determine whether indirect flow forces on arrested tumor cells are likely to impact neighboring endothelial cells. Combination of biophysical tools (such as optical tweezing technologies to manipulate CTC and/or endothelial cells) with microfluidic approaches could be helpful in that regard (Follain et al, 2018a;Harlepp et al, 2017;. In addition, there are obviously additional molecular programs that are likely to be involved during this endothelium-dependent process.…”

Optical trapping in vivo: theory, practice, and applications

“…At such depths, forces applied on circulating RBCs are sufficient to pause the motion of the cell and completely block blood flow in thin blood vessels. Similarly, nanoparticles and microparticles and cells have been manipulated in genetically engineered transparent zebrafish [107,178,179], a relatively small model compared to mice. Zebrafish are of great interest due to its advanced brain structure and its small dimensions [180,181].…”