Integrated Calendar

The heart is a fascinatingly efficient pump with intricate design criteria. While many aspects of heart function remain a mystery, investigations through the prism of mechanics, physics, and mathematics can provide invaluable insights – presented as three examples in this talk. First, we consider the problem of automatically characterizing cardiac tissue architecture over multiple length-scales. Through, the use of existing and creation of new order parameters, multiple discoveries were made such as the existence of consistently sized spontaneous patches of organization in isotropic cardiac tissues. Second, we explore the relationship between cell organization and tissue force generation. Through a tissue engineering trick, the global (~1mm) and local (~100 microns) architecture effects were separated, and it was discovered that the reduction in developed force due purely to changes in global tissue architecture can be predicted by an astonishingly simple physical model, while local changes trigger complex biological responses. Third, we investigate the relationship among genetic mutations to the nuclear lamina protein, Lamin A/C (LMNA), detrimental consequences to cellular architecture, and cardiac function. LMNA mutations can lead to a devastating early aging disease (progeria) or have a subtler effect with patients presenting only with heart disease symptoms. However, the mechanisms by which the LMNA mutation emerges in the heart muscle are unknown. Thus far we have uncovered a relationship between nuclear defects in patient-specific cells and the age at which these patients present with heart disease symptoms. Additionally, we have found that the pathology that takes decades to develop in patients can be recapitulated in a dish within a few weeks. Through all three of these examples, we will also explore newly generated mysteries that can again be elucidated in the future through the application of physical principles.

Cells both actively generate and sensitively react to forces, typically behaving as elastic solids on short
time-scales and resembling a viscous liquid on long time-scales. The long-term behavior is the most
relevant to shaping of tissues. However, measurement of long-term multicellular properties is difficult
because cells are adaptive entities that actively respond to external ques by changing their properties.
Accumulating experimental evidences show that active nematic hydrodynamic theory provides an excellent
framework to help to dissect and understand the complex dynamics across different cell types. In our
recent papers (Nature Physics 2018, Physical Review Letters 2018) [1, 2] we have shown existence of
different nemato-dynamic modes and estimated multicellular physical properties (e.g. activity, viscosity,
friction, Frank elastic constant) using high-throughput screening of in vitro cell cultures. I will present
spontaneous emergence of collective shear flows and activity driven turbulence in cultured tissues. I will
discuss the mechanism behind these phenomena and their effect on cell organization and function

Processes at the interface of inorganic solids and polymers mimic a large variety of natural processes such as stimuli responsive behavior, self-healing, actuation, transport and delivery, pH-buffering, but they are not well understood. Polyelectrolyte multilayers are suitable for studying this, as they can be manipulated at will between glassy, rubbery, hydrogel or organogel. We suggest to investigate photocatalytically triggered local pH changes in titania / polyelectrolyte Layer-by-Layer (LbL) / lipid bilayer assembled interfaces, mimicking natural processes in a novel design strategy for inorganic / polymer interfaces as well as to further brain-inspired computing.
We have shown recently that under irradiation of TiO2 a series of photocatalytic reactions leads to a local change in pH, which modulates the pH sensitive LbL assembly. Prime questions are: (i) how many photons are needed to locally change the pH on titania? (ii) what is the optimum LbL architecture to understand the basis of proton trapping and storage, the pH gradient under local irradiation? And (iii) how to achieve reversible actuation of different assemblies for advanced applications?
We focus for the first time on the possibility of efficient transformation of energy of electromagnetic irradiation into local pH shift to actuate soft matter. This is used to demonstrate the application on cell surface interactions, self-repairing strategies, use of a chemical systems to communicate with bacteria, in general control on non-linear chemical processes at interfaces.

During postimplantation development of the mouse embryo, descendants of the inner cell mass cells in the early epiblast transit from the naïve pluripotent state to the primed pluripotent state. Concurrent with the transition of the pluripotency states is the specification of cell lineages and formation of germ layers in the embryos that serves as the blueprint for embryogenesis. Fate mapping and lineage analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation. The regionalization of cell fates heralding the formation of the basic body plan is conserved in vertebrate embryos at a common phylotypic stage of development. Knowledge of the molecular regulation that underpins the lineage specification and tissue patterning is instrumental for understanding embryonic programming and stem cell-based translational study. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of post-implantation embryo has yet to be undertaken. Here, we reported a spatially resolved transcriptome of cell populations at defined positions in the germ layers over the period of pre- to late gastrulation development. This spatio-temporal transcriptome provides high resolution digitized in situ gene expression profiles and defines the molecular attribute of the genealogy of lineages and continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning in the early postimplantation mouse embryo.

TBA