Ladan Amin

• PhD
• research assistant professor at Boston University

The prion protein is a multifunctional protein that exists in at least two different folding states. It is subject to diverse proteolytic processing steps that lead to prion protein fragments some of which are membrane-bound whereas others are soluble. A multitude of ligands bind to the prion protein and besides proteinaceous binding partners, inte...

The prion protein (PrPC) is a central player in neurodegenerative diseases, such as prion diseases or Alzheimer’s disease. In contrast to disease-promoting cell surface PrPC, extracellular fragments act neuroprotective by blocking neurotoxic disease-associated protein conformers. Fittingly, PrPC release by the metalloprotease ADAM10 represents a pr...

Astrocytes-derived extracellular vesicles (EVs) are key players in glia-neuron communication. However, whether EVs interact with neurons at preferential sites and how EVs reach these sites on neurons remains elusive. Using optical manipulation to study single EV-neuron dynamics, we here show that large EVs scan the neuron surface and use neuronal p...

Several cell-surface receptors for neurotoxic forms of amyloid-β (Aβ) have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating Alzheimer’s disease pathology have remained uncertain. Here, we used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer...

The cellular prion protein (PrPC) is a central player in neurodegenerative diseases caused by protein misfolding, such as prion diseases or Alzheimer's disease (AD). Expression levels of this GPI-anchored glycoprotein, especially at the neuronal cell surface, critically correlate with various pathomechanistic aspects underlying these diseases, such...

Oligomeric forms of amyloid-β (Aβ) peptide are known to be the primary neurotoxic species in Alzheimer , s disease (AD), but how they interact with neurons to produce their deleterious effects is unclear. Over ten different cell-surface receptors for Aβ have been described, but their molecular interactions with Aβ assemblies and their relative cont...

The cellular prion protein (PrP(C)) is a ubiquitous glycoprotein, which is highly expressed in the brain. This protein, mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neurite outgrowth. By using a novel focal stimulation technique, we explored the potential function of PrP(C), in it...

The cellular form of the prion protein (PrP(C)) is a highly conserved glycoprotein mostly expressed in the central and peripheral nervous systems by different cell types in mammals. A misfolded, pathogenic isoform, denoted as prion, is related to a class of neurodegenerative diseases known as transmissible spongiform encephalopathy. PrP(C) function...

We report on the modification of mechanical properties of breast cancer cells when they get in contact with other neighboring cells of the same type. Optical tweezers vertical indentation was employed to investigate cell mechanics in isolated and contact conditions, by setting up stiffness as a marker. Two human breast cancer cell lines with differ...

Extracellular vesicles (EVs) are spherical membrane structures released by most cells. These highly conserved mediators of intercellular communication carry proteins, lipids, and nucleic acids, and transfer these cellular components between cells by different mechanisms, such as endocytosis, macropinocytosis, or fusion. However, the temporal and sp...

Differentiating neurons process the mechanical stimulus by exerting the protrusive forces through lamellipodia and filopodia. We used optical tweezers, video imaging and immunocytochemistry to analyze the role of non-muscle myosin-II on the protrusive force exerted by lamellipodia and filopodia from developing growth cones (GCs) of isolated Dorsal...

Polymerization of actin filaments is the primary source of motility in lamellipodia and it is controlled by a variety of regulatory proteins. The underlying molecular mechanisms are only partially understood and a precise determination of dynamical properties of force generation is necessary. Using optical tweezers, we have measured with millisecon...

Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal...

This file provides additional information about different fixation protocols used for immunostaining of actin and tubulin (Figure S1) and a figure which represent the relation between area of GC and maximum exerted force (Figure S2). (PDF)

Myosin II plays a vital role in many fundamental cellular and developmental processes such as cell-cell adhesion, cell migration and cytokinesis. Using immunocytochemistry, video imaging and optical tweezers we have determined myosin II function in motility and the force exerted by lamellipodia from growth cones (GCs) of isolated Dorsal Root Gangli...

We used optical tweezers to analyze the effect of jasplakinolide and cyclodextrin on the force exerted by lamellipodia from developing growth cones (GCs) of isolated dorsal root ganglia (DRG) neurons. We found that 25 nM of jasplakinolide, which is known to inhibit actin filament turnover, reduced both the maximal exerted force and maximal velocity...

We have used optical tweezers to analyse the effect of Blebbistatin and Cytochalasin D on the force exerted by lamellipodia from developing growth cones of isolated Dorsal Root Ganglia neurons. In the presence of 20 μM Blebbistatin, a well known inhibitor of Myosin II, force generation still occurs but with a slower rate and a reduced velocity of t...

We have used optical tweezers to analyse the effect of Jasplakinolide and Cyclodextrin on the force exerted by lamellipodia from developing growth cones of isolated Dorsal Root Ganglia (DRG) neurons. 25 nM Jasplakinolide, known to reduce actin filament turnover, reduced both the maximal exerted force and maximal velocity with which the lamellipodiu...

We have used optical tweezers to identify the elementary events underlying force generation in neuronal lamellipodia. When an optically trapped bead seals on the lamellipodium membrane, Brownian fluctuations decrease revealing the underlying elementary events. The distribution of bead velocities has long tails with frequent large positive and negat...

Supplementary Information

Polymerization of actin filaments is the primary source of motility in lamellipodia and it is controlled by a variety of regulatory proteins. The underlying molecular mechanisms are only partially understood and a precise determination of dynamical properties of force generation is necessary. Using optical tweezers, we have measured with millisecon...

The propulsion of the leading edge of neuronal lamellipodia is a complex process in which the polymerization of actin filaments towards the cell membrane is a major component (1,2). This process is at the origin of force generation in neurons. By using optical tweezers, we have characterized the dynamics by which lamellipodia of Dorsal Root Ganglia...