Mark Cronin-Golomb

This paper presents an open-source time-dependent three-dimensional scalar photorefractive beam propagation model (PRProp3D) based on the well-known split-step method. The angular spectrum method is used for the diffractive steps, and the nonlinearities accumulated at the end of each diffractive step are applied using spatially varying phase screens. Comparisons with previously published experimental results are given for image amplification, photorefractive amplified scattering (fanning) and photorefractive screening solitons. Artifacts can be mitigated by use of step sizes less than 5~10 micrometers and by careful choice of the transverse computation grid size to ensure adequate sampling. Wraparound effects associated with the use of discrete Fourier transforms are mitigated by apodization and beam centering.

This paper presents an open-source time dependent three-dimensional scalar photorefractive beam propagation model (PRProp3D) based on the well-known split step method. The angular spectrum method is used for the diffractive steps and the nonlinearities accumulated at the end of each diffractive step are applied using spatially varying phase screens. Comparisons with previously published experimental results are given for image amplification and photorefractive amplified scattering (fanning). Artifacts can be mitigated by use of step sizes less than 5~10 micrometers and by careful choice of the transverse computation grid size to ensure adequate sampling. The occurrence of wraparound effects associated with the use of discrete Fourier transforms is discussed.

The electric fields of tightly focused laser beams can be strong enough to apply appreciable force to microscopic objects, including biological entities such as cells, bacteria, and even viruses and biomolecules

Azobenzene modification of Bombyx mori silkworm silk creates a photo-responsive ‘azosilk’ biomaterial, allowing for 3D laser patterning. Written regions fluoresce, and become fluid-filled raised ‘micro-blisters’ with a 10-fold photo-softening effect of the modulus. Patterning is facile and versatile, with potential applications as soft tunable materials for dynamic cell guidance and microfluidics.

Biomechanics plays a central role in breast epithelial morphogenesis. In this study we have used 3D cultures in which normal breast epithelial cells are able to organize into rounded acini and tubular ducts, the main structures found in the breast tissue. We have identified fiber organization as a main determinant of ductal organization. While bulk rheological properties of the matrix seem to play a negligible role in determining the proportion of acini versus ducts, local changes may be pivotal in shape determination. As such, the ability to make microscale rheology measurements coupled with simultaneous optical imaging in 3D cultures can be critical to assess the biomechanical factors underlying epithelial morphogenesis. This paper describes the inclusion of optical tweezers based microrheology in a microscope that had been designed for nonlinear optical imaging of collagen networks in ECM. We propose two microrheology methods and show preliminary results using a gelatin hydrogel and collagen/Matrigel 3D cultures containing mammary gland epithelial cells.

Atomic force microscopes have become indispensable tools for mechanical characterization of nanoscale and submicron structures. However, materials with complex geometries, such as electrospun fiber networks used for tissue scaffolds, still pose challenges due to the influence of tension and bending modulus on the response of the suspended structures. Here we report mechanical measurements on electrospun silk fibers with various treatments that allow discriminating among the different mechanisms that determine the mechanical behavior of these complex structures. In particular we were able to identify the role of tension and boundary conditions (pinned versus clamped) in determining the mechanical response of electrospun silk fibers. Our findings show that high-resolution mechanical imaging with torsional harmonic atomic force microscopy provides a reliable method to investigate the mechanics of materials with complex geometries.

The chimeric proteins, silk–elastin-like protein polymers (SELPs), consist of repeating units of silk and elastin to retain the mechanical strength of silk, while incorporating the dynamic environmental sensitivity of elastin. A retinal-modified SELP was prepared, modified, and studied for photodynamic responses. The protein was designed, cloned, expressed, and purified with lysine present in the elastin repeats. The purified protein was then chemically modified with the biocompatible moiety retinal via the lysine side chains. Structural changes with the polymer were assessed before and after retinal modification using Fourier transform infrared spectroscopy and circular dichroism spectroscopy. Optical studies and spectral analysis were performed before and after retinal modification. The random-coil fraction of the protein increased after retinal modification while the β-sheet fraction significantly decreased. Birefringence of the modified protein was induced when irradiated with a linearly polarized 488 nm laser light. Retinal modification of this protein offers a useful strategy for potential use in biosensors, controlled drug delivery, and other areas of biomedical engineering.

Electric fields are integral to many biological events, from maintaining cellular homeostasis to embryonic development to healing. The application of electric fields offers substantial therapeutic potential, while optimal dosing regimens and the underlying mechanisms responsible for the positive clinical impact are poorly understood. The purpose of this study was to track the differentiation profile and stress response of human bone marrow derived mesenchymal stem cells (hMSCs) undergoing osteogenic differentiation during exposure to a 20 mV/cm, 60 kHz electric field. Morphological and biochemical changes were imaged using endogenous two-photon excited fluorescence (TPEF) and quantitatively assessed through eccentricity calculations and extraction of the redox ratio from NADH, FAD and lipofuscin contributions. Real time reverse transcriptase-polymerase chain reactions (RT-PCR) were used to track osteogenic differentiation markers, namely alkaline phosphatase (ALP) and collagen type 1 (col1), and stress response markers, such as heat shock protein 27 (hsp27) and heat shock protein 70 (hsp70). Comparisons of collagen deposition between the stimulated hMSCs and controls were examined through second harmonic generation (SHG) imaging. Quantitative differences in cell morphology, as described through an eccentricity ratio, were found on days 2 and days 5 (p < 0.05) in samples exposed to the electric field. A delayed but two fold increase in ALP and col1 transcript was detected by week 2 (p < 0.05) in differentiating hMSCs exposed to an electric field in comparison to the nonstimulated controls. Upregulation in stress marker, hsp27, and type 1 collagen deposition were correlated with this response. Increases in NADH, FAD, and lipofuscin were traced in the stimulation group during the first week of field exposure with differences statistically significant on day 10 (p < 0.05). Changes in hsp27 expression correlate well with changes in lipofuscin detected in the stimulation group, suggesting a connection with oxidative stress. Both differentiation factors and electrical stimulation improved hMSC differentiation potential to bone based on calcium deposition on day 28. Electrical stimulation is a useful tool to improve hMSC osteogenic differentiation, while heat shock proteins may reveal underlying mechanisms, and optical non-invasive imaging may be used to monitor the induced morphological and biochemical changes.

We report a novel method for characterizing the stiffness of white light supercontinuum tweezers, in which the nonlinear photonic crystal fiber used for supercontinuum generation is also utilized as an effective confocal pinhole to track the motion of a trapped bead and as a scan head to realize rapid scanning of the optical trap. By measuring the phase of the bead's motion in following the trap, a lateral stiffness value of about 7.9 μN/m was obtained with supercontinumm power of about 75 mW. Our technique can potentially allow for trap stiffness calibration along an arbitrary direction in three dimensions.