Numerous hypotheses invoke tissue stiffness as a key parameter that regulates morphogenesis and disease progression. However, current methods are insufficient to test hypotheses that concern physical properties deep in living tissues. Here we introduce, validate, and apply a magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate an organ-stage mouse embryo under live conditions. The method allows rapid, nontoxic measurement of the three-dimensional (3D) spatial distribution of viscoelastic properties within mesenchyme and epithelia. Using the device, we identify an anteriorly biased mesodermal stiffness gradient along which cells move to shape the early limb bud. The stiffness gradient corresponds to aWnt5a-dependent domain of fibronectin expression, raising the possibility that durotaxis underlies cell movements. Three-dimensional stiffness mapping enables the generation of hypotheses and potentially the rigorous testing of mechanisms of development and disease.
From
single-pole magnetic tweezers to robotic magnetic-field generation
systems, the development of magnetic micromanipulation systems, using
electromagnets or permanent magnets, has enabled a multitude of applications
for cellular and intracellular measurement and stimulation. Controlled
by different configurations of magnetic-field generation systems,
magnetic particles have been actuated by an external magnetic field
to exert forces/torques and perform mechanical measurements on the
cell membrane, cytoplasm, cytoskeleton, nucleus, intracellular motors, etc. The particles have also been controlled to generate
aggregations to trigger cell signaling pathways and produce heat to
cause cancer cell apoptosis for hyperthermia treatment. Magnetic micromanipulation
has become an important tool in the repertoire of toolsets for cell
measurement and stimulation and will continue to be used widely for
further explorations of cellular/intracellular structures and their
functions. Existing review papers in the literature focus on fabrication
and position control of magnetic particles/structures (often termed
micronanorobots) and the synthesis and functionalization of magnetic
particles. Differently, this paper reviews the principles and systems
of magnetic micromanipulation specifically for cellular and intracellular
measurement and stimulation. Discoveries enabled by magnetic measurement
and stimulation of cellular and intracellular structures are also
summarized. This paper ends with discussions on future opportunities
and challenges of magnetic micromanipulation in the exploration of
cellular biophysics, mechanotransduction, and disease therapeutics.
Inspired by the collective intelligence in natural swarms, microrobotic agents have been controlled to form artificial swarms for targeted drug delivery, enhanced imaging, and hyperthermia. Different from these well-investigated tasks, this work aims to develop microrobotic swarms for embolization, which is a clinical technique used to block blood vessels for treating tumors, fistulas, and arteriovenous malformations. Magnetic particle swarms were formed for selective embolization to address the low selectivity of the present embolization technique that is prone to cause complications such as stroke and blindness. We established an analytical model that describes the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, based on which an actuation strategy was developed to maintain the swarm integrity inside a targeted region under fluidic flow conditions. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.
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