# SPOTs: Optical Technologies for Instantly Quantifying Multicellular Response Profiles

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $530,374

## Abstract

PROJECT SUMMARY/ABSTRACT
Human organ systems require temporally and spatially coordinated multicellular actions at a macroscale to
actuate, sustain, or terminate dedicated and vital functions. Cells that comprise discrete or distributed
physiologic systems that fail to respond to appropriate stimuli with coordination may cause significant morbidity
and often mortality. Collective and coordinated physiologic activities typically involve millions to billions of cells
that may span large physical distances. Technologies for quantifying the electrical, chemical, and mechanical
coupling in these multicellular systems are critically important to understanding the underlying mechanisms of
disease and develop therapeutic approaches. However, no technology currently exists to quantify rapid
mechanical cell responses to transmitted distal perturbations for all cells within a collection of cells. This multi-
PI proposal (Chiou (contact PI) and Teitell) aims to develop a new platform imaging technology called SPOT
(single pixel optical technology) for concurrent and direct measurements of cellular traction forces over a 1.0 x
1.0 cm2 field of view (FOV) with cellular spatial resolution, and a 1,000 frames/sec temporal resolution. SPOT
provides a 4-order of magnitude larger FOV than conventional traction force microscopy. Cardiomyocytes
(CMs) are the test bed here because of a high potential for impact in cardiovascular disease, the leading cause
of mortality in the Western World. We will demonstrate the ability for SPOT to determine quantitative indices of
abnormalities for human CM contraction and relaxation in healthy and diseased states. We will establish proof
of concept studies in SPOT screens for small molecules that augment or affect CM contraction in desmoplakin
deficient states. We will build a platform that integrates SPOT for direct contraction force measurements and
Optical Mapping for electrical property measurements for sheets of CMs. This will enable, for the first time,
studies of temporal and spatial electromechanical coupling behaviors for sheets of CMs at single cell
resolution. We will distinguish different subtypes of CMs, their distributions, their interactions, and their
phenotypic responses under external perturbations. And we will apply this platform to investigate the structural
and electromechanical coupling properties of hESC-derived CMs by integrating quantitative biomass and
stiffness data measured using non-invasive live cell interferometry (LCI). Changes in biomass and cell stiffness
are druggable biophysical parameters with correlates to mechanical contraction/relaxation cycles of CMs. In
addition to detailed studies of CMs that have the potential to impact the number one killer of US citizens, SPOT
applications should have utility and provide new insights in additional settings that require cell or tissue
traction-force generation. Such settings could include models in a dish for wound healing, cancer cell
metastasis, or mod...

## Key facts

- **NIH application ID:** 9972477
- **Project number:** 1R01GM127985-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Pei-Yu Chiou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $530,374
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972477

## Citation

> US National Institutes of Health, RePORTER application 9972477, SPOTs: Optical Technologies for Instantly Quantifying Multicellular Response Profiles (1R01GM127985-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972477. Licensed CC0.

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