Characterizing deformability and surface friction of cancer cells.
Proceedings of the National Academy of Sciences of the United States of America
2013; 110 (19): 7580-7585
Mapping a Complete Neural Population in the Retina
JOURNAL OF NEUROSCIENCE
2012; 32 (43): 14859-14873
Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell's passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its frictional properties with the channel wall. Here, we introduce a device that enables the precise measurement of (i) the size of a single cell, given by its buoyant mass, (ii) the velocity of the cell entering a constricted microchannel (entry velocity), and (iii) the velocity of the cell as it transits through the constriction (transit velocity). Changing the deformability of the cell by perturbing its cytoskeleton primarily alters the entry velocity, whereas changing the surface friction by immobilizing positive charges on the constriction's walls primarily alters the transit velocity, indicating that these parameters can give insight into the factors affecting the passage of each cell. When accounting for cell buoyant mass, we find that cells possessing higher metastatic potential exhibit faster entry velocities than cells with lower metastatic potential. We additionally find that some cell types with higher metastatic potential exhibit greater than expected changes in transit velocities, suggesting that not only the increased deformability but reduced friction may be a factor in enabling invasive cancer cells to efficiently squeeze through tight spaces.
View details for DOI 10.1073/pnas.1218806110
View details for PubMedID 23610435
A cross-platform toolkit for mass spectrometry and proteomics
2012; 30 (10): 918-920
Low error discrimination using a correlated population code
JOURNAL OF NEUROPHYSIOLOGY
2012; 108 (4): 1069-1088
Recording simultaneously from essentially all of the relevant neurons in a local circuit is crucial to understand how they collectively represent information. Here we show that the combination of a large, dense multielectrode array and a novel, mostly automated spike-sorting algorithm allowed us to record simultaneously from a highly overlapping population of >200 ganglion cells in the salamander retina. By combining these methods with labeling and imaging, we showed that up to 95% of the ganglion cells over the area of the array were recorded. By measuring the coverage of visual space by the receptive fields of the recorded cells, we concluded that our technique captured a neural population that forms an essentially complete representation of a region of visual space. This completeness allowed us to determine the spatial layout of different cell types as well as identify a novel group of ganglion cells that responded reliably to a set of naturalistic and artificial stimuli but had no measurable receptive field. Thus, our method allows unprecedented access to the complete neural representation of visual information, a crucial step for the understanding of population coding in sensory systems.
View details for DOI 10.1523/JNEUROSCI.0723-12.2012
View details for Web of Science ID 000310523900003
View details for PubMedID 23100409
Computation of uniform wave forms using complex rays
PHYSICAL REVIEW E
2006; 73 (3)
We explored the manner in which spatial information is encoded by retinal ganglion cell populations. We flashed a set of 36 shape stimuli onto the tiger salamander retina and used different decoding algorithms to read out information from a population of 162 ganglion cells. We compared the discrimination performance of linear decoders, which ignore correlation induced by common stimulation, with nonlinear decoders, which can accurately model these correlations. Similar to previous studies, decoders that ignored correlation suffered only a modest drop in discrimination performance for groups of up to ?30 cells. However, for more realistic groups of 100+ cells, we found order-of-magnitude differences in the error rate. We also compared decoders that used only the presence of a single spike from each cell with more complex decoders that included information from multiple spike counts and multiple time bins. More complex decoders substantially outperformed simpler decoders, showing the importance of spike timing information. Particularly effective was the first spike latency representation, which allowed zero discrimination errors for the majority of shape stimuli. Furthermore, the performance of nonlinear decoders showed even greater enhancement compared with linear decoders for these complex representations. Finally, decoders that approximated the correlation structure in the population by matching all pairwise correlations with a maximum entropy model fit to all 162 neurons were quite successful, especially for the spike latency representation. Together, these results suggest a picture in which linear decoders allow a coarse categorization of shape stimuli, whereas nonlinear decoders, which take advantage of both correlation and spike timing, are needed to achieve high-fidelity discrimination.
View details for DOI 10.1152/jn.00564.2011
View details for Web of Science ID 000308000500011
View details for PubMedID 22539825
Mirrors with regular hexagonal segments
2003; 42 (25): 5130-5135
Complex rays and polynomial phase functions are used to numerically solve the Helmholtz equation in a realistic two-dimensional smoothly varying heterogeneous velocity model with multiple adjacent cusp caustics. Together these two methods allow the determination of global uniformly asymptotic solutions in the presence of arbitrarily many caustics. Two algorithms are introduced to this end: a two-point ray tracing algorithm for complex rays and a perturbation method for constructing polynomial phase functions. Model representation in complex space is performed via discrete cosine transform analysis. Geometrical and uniformly asymptotic solutions are computed for a linear layer test model as well as a velocity model from Yucca Mountain.
View details for DOI 10.1103/PhysRevE.73.036704
View details for Web of Science ID 000236467700113
View details for PubMedID 16605695
The point-spread function and emissivity are calculated for a mirror made from regular hexagonal segments of just a few different sizes. A mirror of this type has many similar segments, which is an advantage for manufacturing, and for an approximately f/1 mirror with > or = 1000 segments and > or = 4 sizes of regular hexagons the increase in intersegment gap area is negligible. This result raises the possibility of making a mirror from very large numbers of identical small segments that are warped to the required figure.
View details for Web of Science ID 000184963200019
View details for PubMedID 12962392